thescientist--2020-12-09--Distinct Microbiome and Metabolites Linked with Depression

The human gut microbiome is a world in miniature , populated by a chatty community of bacteria , viruses , fungi , and protozoa nestled within various gastrointestinal niches .
Over the past decade , researchers have linked disturbances within this complicated microbial society to a variety of diseases .
Major depressive disorder ( MDD ) is one such condition , but the studies have been small and the findings imprecise .
A study published December 2 in Science Advances changes all that with its vivid description of a distinct microbiome associated with major depressive disorder , as well as @ @ @ @ @ @ @ .
The researchers were able to use this microbial “ fingerprint ” to distinguish between individuals with MDD and healthy controls , solely on the composition of a few microbes and compounds in their fecal matter .
“ What this paper does is bring the complexity of the ecology of the microbiome into focus , ” says neuroscientist John Cryan at APC Microbiome Ireland and University College Cork who was not part of the study team .
“ It ’ s a welcome addition to the field.
” “ The strength of the @ @ @ @ @ @ @ the metagenomics to identify the key taxa as well as the metabolites , because in the end we need to link whatever the biosignature of the taxa are to the host , ” McMaster University ’ s Jane Foster , who was not part of the study , tells The Scientist .
She adds that it ’ s one of the first studies to conduct metagenomics and metabolomics in the same sample for depression .
Microbiome researchers studying MDD have been using an inexact technique called 16S ribosomal RNA sequencing , which can @ @ @ @ @ @ @ level within a batch of microorganisms , and it excludes viruses .
But psychiatrist Shaohua Hu at Zhejiang University School of Medicine in China and his group wanted a more precise picture of the organisms present , so they gathered fecal samples from 236 people , half of whom had been diagnosed with MDD and were unmedicated , and half who were healthy .
They sequenced the total genomic DNA of all the bacteria and viruses in the samples , and then used statistical programs to analyze the differences and similarities between people @ @ @ @ @ @ @ found that 18 bacterial species were more abundant in people with MDD ( mainly belonging to the genus Bacteroides ) and 29 were less common ( primarily the genera Blautia and Eubacterium ) compared to healthy controls .
Hu and his team also found three bacteriophages ( viruses that infect bacteria ) whose levels were different in MDD versus healthy controls , the first time the virome has been studied in MDD .
Sequencing entire microbial genomes allowed the team to distinguish between organisms that are genetically similar , but functionally very unique @ @ @ @ @ @ @ , researcher Carra Simpson in an email .
“ Compared to the commonly employed marker gene sequencing approaches , [ the authors ] have greater resolution to distinguish these species and within a comparatively large sample size.
” This helps to “ elucidate the functional implications of bacterial alterations on the host.
” To determine the effect of these changes , Hu and the group analyzed the so-called “ functional readout ” —the molecules the microorganisms produce—of the entire gut microbiome using gas chromatography-mass spectrometry ( GC-MS ) .
It turns out that @ @ @ @ @ @ @ metabolites and less of 34 compounds than did healthy controls ; most of these molecules were involved in amino acid metabolism .
The three most important pathways were related to gamma-aminobutyric acid ( GABA ) metabolism , phenylalanine metabolism , and tryptophan metabolism .
Hu ’ s team then created a biomarker panel consisting of two species of bacteria , two types of bacteriophage viruses , and two different metabolites .
In a separate group of 75 subjects ( half with MDD , half healthy controls ) , the biomarker panel was able @ @ @ @ @ @ @ around 90 percent of the time .
The researchers point out that GABA is a neurotransmitter in the brain , but it ’ s also made by gut microbes ; fecal levels of GABA and certain of its metabolites were decreased in the MDD patients , and the team also found that GABA-related microbial genes were altered in MDD patients , suggesting that microbes modulate GABA levels .
Hu and his team hypothesize that this may dysregulate the function of GABA in the brain , and could lead to depressive symptoms .
In @ @ @ @ @ @ @ the increase in Bacteroides bacteria , which induce cytokine production , could increase inflammation , a condition that has been linked to MDD .
Also , decreased Blautia , which has been shown to have anti-inflammatory effects , could contribute to MDD .
Other studies have also found that when researchers transplant the entire microbiota of a person with MDD into a germ-free rat , the rat starts to behave depressed .
These are speculative assertions , and Hu says this one cross-sectional study can ’ t determine causality , and rather , @ @ @ @ @ @ @ bi-directional axis .
The depressed symptoms can influence our diet behavior , so it can influence our gut characteristics and composition , and also on the other side , our bacteria can produce some special metabolites and have a special pathway that can influence our brain function.
” “ This sets the scene for a lot more work to validate whether any of these pathways are actually causally related to depression , ” says Cryan , who receives research funding from Dupont Nutrition , Cremo SA , and Nutricia Danone .
“ There @ @ @ @ @ @ @ nutritional psychiatry right now .
Can we target the microbiome through diet , could we alleviate some of the effects of depression ?
” J. Yang et al.
, “ Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders , ” Science Advances , 6 : eaba8555 , 2020 .

ABOVE: © ISTOCK.COM, LUISMMOLINA
The human gut microbiome is a world in miniature, populated by a chatty community of bacteria, viruses, fungi, and protozoa nestled within various gastrointestinal niches. Over the past decade, researchers have linked disturbances within this complicated microbial society to a variety of diseases. Major depressive disorder (MDD) is one such condition, but the studies have been small and the findings imprecise. A study published December 2 in Science Advances changes all that with its vivid description of a distinct microbiome associated with major depressive disorder, as well as the profile of molecules these organisms produce. The researchers were able to use this microbial “fingerprint” to distinguish between individuals with MDD and healthy controls, solely on the composition of a few microbes and compounds in their fecal matter.
“What this paper does is bring the complexity of the ecology of the microbiome into focus,” says neuroscientist John Cryan at APC Microbiome Ireland and University College Cork who was not part of the study team. “It’s a welcome addition to the field.”
“The strength of the paper is this dual approach to both the metagenomics to identify the key taxa as well as the metabolites, because in the end we need to link whatever the biosignature of the taxa are to the host,” McMaster University’s Jane Foster, who was not part of the study, tells The Scientist. She adds that it’s one of the first studies to conduct metagenomics and metabolomics in the same sample for depression.
Microbiome researchers studying MDD have been using an inexact technique called 16S ribosomal RNA sequencing, which can identify bacteria only down to the genus level within a batch of microorganisms, and it excludes viruses. But psychiatrist Shaohua Hu at Zhejiang University School of Medicine in China and his group wanted a more precise picture of the organisms present, so they gathered fecal samples from 236 people, half of whom had been diagnosed with MDD and were unmedicated, and half who were healthy. They sequenced the total genomic DNA of all the bacteria and viruses in the samples, and then used statistical programs to analyze the differences and similarities between people with MDD and healthy controls.
The depressed symptoms can influence our diet behavior, so it can influence our gut characteristics and composition, and also on the other side, our bacteria can produce some special metabolites and have a special pathway that can influence our brain function. —Shaohua Hu, Zhejiang University School of Medicine
They found that 18 bacterial species were more abundant in people with MDD (mainly belonging to the genus Bacteroides) and 29 were less common (primarily the genera Blautia and Eubacterium) compared to healthy controls. Hu and his team also found three bacteriophages (viruses that infect bacteria) whose levels were different in MDD versus healthy controls, the first time the virome has been studied in MDD.
Sequencing entire microbial genomes allowed the team to distinguish between organisms that are genetically similar, but functionally very unique, writes University of Melbourne, Australia, researcher Carra Simpson in an email. “Compared to the commonly employed marker gene sequencing approaches, [the authors] have greater resolution to distinguish these species and within a comparatively large sample size.” This helps to “elucidate the functional implications of bacterial alterations on the host.”
To determine the effect of these changes, Hu and the group analyzed the so-called “functional readout”—the molecules the microorganisms produce—of the entire gut microbiome using gas chromatography-mass spectrometry (GC-MS). It turns out that MDD patients harbored significantly more of 16 metabolites and less of 34 compounds than did healthy controls; most of these molecules were involved in amino acid metabolism. The three most important pathways were related to gamma-aminobutyric acid (GABA) metabolism, phenylalanine metabolism, and tryptophan metabolism.
Hu’s team then created a biomarker panel consisting of two species of bacteria, two types of bacteriophage viruses, and two different metabolites. In a separate group of 75 subjects (half with MDD, half healthy controls), the biomarker panel was able to accurately pick out those with depression around 90 percent of the time.
Possible microbial effects on depression—and vice versa
The researchers point out that GABA is a neurotransmitter in the brain, but it’s also made by gut microbes; fecal levels of GABA and certain of its metabolites were decreased in the MDD patients, and the team also found that GABA-related microbial genes were altered in MDD patients, suggesting that microbes modulate GABA levels. Hu and his team hypothesize that this may dysregulate the function of GABA in the brain, and could lead to depressive symptoms.
In addition, the scientists hypothesize that perhaps the increase in Bacteroides bacteria, which induce cytokine production, could increase inflammation, a condition that has been linked to MDD. Also, decreased Blautia, which has been shown to have anti-inflammatory effects, could contribute to MDD. Other studies have also found that when researchers transplant the entire microbiota of a person with MDD into a germ-free rat, the rat starts to behave depressed.
These are speculative assertions, and Hu says this one cross-sectional study can’t determine causality, and rather, “I think it’s a bi-directional axis. The depressed symptoms can influence our diet behavior, so it can influence our gut characteristics and composition, and also on the other side, our bacteria can produce some special metabolites and have a special pathway that can influence our brain function.”
“This sets the scene for a lot more work to validate whether any of these pathways are actually causally related to depression,” says Cryan, who receives research funding from Dupont Nutrition, Cremo SA, and Nutricia Danone. “There’s a whole emerging field in nutritional psychiatry right now. Can we target the microbiome through diet, could we alleviate some of the effects of depression?”
J. Yang et al., “Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders,” Science Advances, 6:eaba8555, 2020.


thescientist--2020-12-11--Humans Domesticated Yeast Through Bread-Making: Study

east is not typically considered a domesticated organism .
Dogs , cats , and cows might come to mind first , but humans have nonetheless played an important role in the fungus ’ s evolution .
A study in Current Biology published yesterday ( December 9 ) reports that humans have caused most bread yeast strains , Saccharomyces cerevisiae , to diverge into two distinct groups : one used in large-scale , industrial bread-making and one used in artisanal sourdough bread .
While industrial strains start fermenting more quickly , sourdough yeasts have more copies of the genes responsible for @ @ @ @ @ @ @ happens later in the fermentation process and helps leaven the dough .
“ It ’ s a good paper , ” says Pacific Northwest Research Institute senior investigator Aimée Dudley , who studies yeast genetics and was not involved in the study .
“ It makes sense with what we know about how people have been baking bread historically , ” referring to the priority of speed in commercial bread-making compared to that of artisanal bakers .
Bread is universal and has been for millennia , explains Sicard , but with a dramatic @ @ @ @ @ @ @ industrial era , her team wanted to understand how these changes have shaped yeast ’ s evolution .
Yeast domestication has been studied in other food and beverages—cheese , wine , and beer , for example—but not in breads .
French National Research Institute for Agriculture evolutionary geneticist Delphine Sicard , a coauthor of the study , says bread yeasts have seldom been studied because many of these yeast strains are tetraploids , cells that contain four homologous sets of chromosomes , which makes studying their population genetics more complicated than studying diploids @ @ @ @ @ @ @ obtained 198 sourdough strains from France , Belgium , and Italy and 31 commercial strains from starter kits or international yeast collections .
They analyzed the number of chromosome sets in each of these strains using flow cytometry and investigated the genetic diversity of diploids and tetraploids using microsatellite marker analysis .
Sicard and her colleagues then analyzed the newly sequenced genomes of 17 bakery yeast strains and 1,011 other S. cerevisiae strains described in a 2018 Nature study , which includes 51 bakery strains , to create a phylogenetic tree and map @ @ @ @ @ @ @ found that sourdough strains typically contained a higher copy number of genes that encode proteins that transport and regulate maltase and isomaltase as well as the enzymes themselves , which break down the sugars maltose and isomaltose .
Abnormalities in copy number can be harmful to cells , but the authors explain that they can also enable rapid adaptation in a period of stringent selection , such as proliferating in the toxic high–maltose and isomaltose environment of wheat flour that ’ s used in making sourdough bread .
The researchers found that , @ @ @ @ @ @ @ maltose as a carbon source , yeast that had more copies of these genes were more abundant by the end of fermentation than were yeasts that had fewer copies .
Whether bakers deliberately passed on sourdough starters that they thought would work best or the yeast evolved to adapt to their environments , the end result is that sourdough yeast is well-suited for making specifically sourdough bread , explains Sicard .
“ This is a nice example of a domestication genetic signature , ” Sicard says .
Meanwhile , industrial bakers appear to @ @ @ @ @ @ @ quickly—producing 1 g of carbon dioxide after inoculation about half an hour earlier than sourdough yeasts do , on average , in the study—prioritizing the breakdown of glucose over more complex sugars such as maltose and isomaltose that would take more time to break down .
Both industrial and sourdough strains started fermentation more quickly than all other yeasts analyzed , including beer and wine strains .
Dudley points out that sourdough starter contains other microbes , such as lactic acid bacteria and other yeasts , that form complex interactions with the S. @ @ @ @ @ @ @ to see future work that examines these relationships to understand how they may be contributing to the domestication of S. cerevisiae .
Historians and scientists have long theorized that beer brewers and bakers have historically exchanged their yeasts , and the results of the study add some weight to the idea : a group of yeast strains that the researchers in the Nature study associated with African beer contains sourdough strains isolated from Ghanaian maize dough , suggesting that the same strains were historically used both to ferment maize dough and to brew @ @ @ @ @ @ @ report that another clade identified in the Nature study contains beer strains , commercial bakery strains from all over the world , and a few of the newly sequenced sourdough strains from Belgium and France .
Meanwhile , all but three bakery strains clustered separately from wine and sake lineages , suggesting distinct evolutionary histories .
Yeast is found just about everywhere , making it a daunting task to categorize yeast strains , says Edward Louis , the director of the Centre for Genetic Architecture of Complex Traits at the University of Leicester @ @ @ @ @ @ @ study .
Only approximately two-thirds of the analyzed yeast strains Sicard ’ s team analyzed could be grouped into the industrial and artisanal sourdough clades—and even among these , there were many “ mosaic strains ” that included characteristics of both .
“ Is there really domestication or are we just taking advantage of natural variation that ’ s out there or moving yeast around to generate new diversity that just happens to fit whatever environment we ’ re throwing at them ?
” Louis asks .
Still , he says the finding @ @ @ @ @ @ @ the industrial strains is compelling evidence , as those properties most likely wouldn ’ t give yeast an advantage on oak tree bark or soil , where S. cerevisiae is found in the wild , for example .
Sicard says she worries that industrial bread-making could lower the amount of diversity found in yeast strains , but that she is encouraged by the resurgence of homemade bread baking over the past decade , and especially during the COVID-19 pandemic .
“ With this renewed interest in sourdough bread , we may be able @ @ @ @ @ @ @ future , at least in this food chain , ” she says .
“ It ’ s tough to make bread , and if we can , as scientists , add value to bakers ’ work , then it would be great.
” Louis says that this study helps capture the genetic diversity of bread yeasts , which is an important step toward preserving it .
“ By going the commercial route and replacing it all with one or two types , we ’ ll still have good bread and beer , but @ @ @ @ @ @ @ of the nice things about it , ” he says .
F. Bigey et al.
, “ Evidence for two main domestication trajectories in Saccharomyces cerevisiae linked to distinct bread-making processes , ” Current Biology , doi:10.1016/j.cub.2020.11.016 , 2020 .

ABOVE: © ISTOCK.COM,
SEDAEVA
Y
east is not typically considered a domesticated organism. Dogs, cats, and cows might come to mind first, but humans have nonetheless played an important role in the fungus’s evolution. A study in Current Biology published yesterday (December 9) reports that humans have caused most bread yeast strains, Saccharomyces cerevisiae, to diverge into two distinct groups: one used in large-scale, industrial bread-making and one used in artisanal sourdough bread. While industrial strains start fermenting more quickly, sourdough yeasts have more copies of the genes responsible for metabolizing maltose, a process that typically happens later in the fermentation process and helps leaven the dough.
“It’s a good paper,” says Pacific Northwest Research Institute senior investigator Aimée Dudley, who studies yeast genetics and was not involved in the study. “It makes sense with what we know about how people have been baking bread historically,” referring to the priority of speed in commercial bread-making compared to that of artisanal bakers.
Bread is universal and has been for millennia, explains French National Research Institute for Agriculture evolutionary geneticist Delphine Sicard, a coauthor of the study, but with a dramatic shift toward mass-produced yeast starters in the industrial era, her team wanted to understand how these changes have shaped yeast’s evolution. Yeast domestication has been studied in other food and beverages—cheese, wine, and beer, for example—but not in breads. Sicard says bread yeasts have seldom been studied because many of these yeast strains are tetraploids, cells that contain four homologous sets of chromosomes, which makes studying their population genetics more complicated than studying diploids or haploids.
Historians and scientists have long theorized that beer brewers and bakers have historically exchanged their yeasts, and the results of the study add some weight to the idea.
Sicard’s team obtained 198 sourdough strains from France, Belgium, and Italy and 31 commercial strains from starter kits or international yeast collections. They analyzed the number of chromosome sets in each of these strains using flow cytometry and investigated the genetic diversity of diploids and tetraploids using microsatellite marker analysis. Sicard and her colleagues then analyzed the newly sequenced genomes of 17 bakery yeast strains and 1,011 other S. cerevisiae strains described in a 2018 Nature study, which includes 51 bakery strains, to create a phylogenetic tree and map copy number variations along it.
They found that sourdough strains typically contained a higher copy number of genes that encode proteins that transport and regulate maltase and isomaltase as well as the enzymes themselves, which break down the sugars maltose and isomaltose. Abnormalities in copy number can be harmful to cells, but the authors explain that they can also enable rapid adaptation in a period of stringent selection, such as proliferating in the toxic high–maltose and isomaltose environment of wheat flour that’s used in making sourdough bread.
The researchers found that, in a synthetic sourdough environment with only maltose as a carbon source, yeast that had more copies of these genes were more abundant by the end of fermentation than were yeasts that had fewer copies. Whether bakers deliberately passed on sourdough starters that they thought would work best or the yeast evolved to adapt to their environments, the end result is that sourdough yeast is well-suited for making specifically sourdough bread, explains Sicard. “This is a nice example of a domestication genetic signature,” Sicard says.
Meanwhile, industrial bakers appear to have selected yeasts that start fermentation more quickly—producing 1 g of carbon dioxide after inoculation about half an hour earlier than sourdough yeasts do, on average, in the study—prioritizing the breakdown of glucose over more complex sugars such as maltose and isomaltose that would take more time to break down. Both industrial and sourdough strains started fermentation more quickly than all other yeasts analyzed, including beer and wine strains.
Dudley points out that sourdough starter contains other microbes, such as lactic acid bacteria and other yeasts, that form complex interactions with the S. cerevisiae, so she says she hopes to see future work that examines these relationships to understand how they may be contributing to the domestication of S. cerevisiae.
With this renewed interest in sourdough bread, we may be able to conserve more microbial diversity in the future, at least in this food chain. —Delphine Sicard, French National Institute for Agriculture, Food, and Environment
Historians and scientists have long theorized that beer brewers and bakers have historically exchanged their yeasts, and the results of the study add some weight to the idea: a group of yeast strains that the researchers in the Nature study associated with African beer contains sourdough strains isolated from Ghanaian maize dough, suggesting that the same strains were historically used both to ferment maize dough and to brew beer. Sicard and her colleagues also report that another clade identified in the Nature study contains beer strains, commercial bakery strains from all over the world, and a few of the newly sequenced sourdough strains from Belgium and France. Meanwhile, all but three bakery strains clustered separately from wine and sake lineages, suggesting distinct evolutionary histories.
Yeast is found just about everywhere, making it a daunting task to categorize yeast strains, says Edward Louis, the director of the Centre for Genetic Architecture of Complex Traits at the University of Leicester who was not involved in the latest study. Only approximately two-thirds of the analyzed yeast strains Sicard’s team analyzed could be grouped into the industrial and artisanal sourdough clades—and even among these, there were many “mosaic strains” that included characteristics of both.
“Is there really domestication or are we just taking advantage of natural variation that’s out there or moving yeast around to generate new diversity that just happens to fit whatever environment we’re throwing at them?” Louis asks. Still, he says the finding about the quick rate of fermentation among the industrial strains is compelling evidence, as those properties most likely wouldn’t give yeast an advantage on oak tree bark or soil, where S. cerevisiae is found in the wild, for example.
Sicard says she worries that industrial bread-making could lower the amount of diversity found in yeast strains, but that she is encouraged by the resurgence of homemade bread baking over the past decade, and especially during the COVID-19 pandemic. “With this renewed interest in sourdough bread, we may be able to conserve more microbial diversity in the future, at least in this food chain,” she says. “It’s tough to make bread, and if we can, as scientists, add value to bakers’ work, then it would be great.”
Louis says that this study helps capture the genetic diversity of bread yeasts, which is an important step toward preserving it. “By going the commercial route and replacing it all with one or two types, we’ll still have good bread and beer, but we’re probably losing a lot of the nice things about it,” he says.
F. Bigey et al., “Evidence for two main domestication trajectories in Saccharomyces cerevisiae linked to distinct bread-making processes,” Current Biology, doi:10.1016/j.cub.2020.11.016, 2020.


thescientist--2020-12-11--Gene Therapy in One Eye Improves Vision in Both Eyes

ABOVE : Illustration of a mitochondrion .
A genetic variant in the mitochondrial genome is responsible for Leber hereditary optic neuropathy .
© ISTOCK.COM , TUSSIK1 n a Phase 3 gene therapy trial intended to improve vision among patients with Leber hereditary optic neuropathy , recipients gained somewhat better sight in both eyes even though only one was treated .
The results and an investigation into possible explanations for the findings were published December 9 in Science Translational Medicine .
The paper “ has very strong clinical implications that a single injection maybe is enough for bilateral effects , ” @ @ @ @ @ @ @ gene therapy at Aarhaus University in Denmark and was not involved in the work .
The onset of Leber hereditary optic neuropathy ( LHON ) is sudden .
Patients—usually young men—start losing vision at the center of one eye .
Within months , the other eye follows , leaving them legally blind .
The disease is caused by a point mutation in the mitochondrial genome that leads to dysfunction and death of retinal ganglion cells , the axons of which make up the optic nerve .
About 70 percent of patients have the @ @ @ @ @ @ @ “ If you 're going to start somewhere , it makes sense to tackle this variant , ” says Patrick Yu-Wai-Man , an ophthalmologist at the University of Cambridge in the United Kingdom .
He and his collaborators , including teams from GenSight Biologics and Stealth Biotherapeutics and a group led by University of Pittsburg Medical Center ophthalmologist José-Alain Sahel , as well as other groups , previously showed that the point mutation could be corrected in animal models and in cell culture using gene therapy .
It ’ s difficult to get @ @ @ @ @ @ @ mitochondria have two membranes , an outer and inner membrane , Yu-Wai-Man explains .
In the clinical trial , he , Sahel , and colleagues overcame this hurdle by injecting an AAV vector containing a wildtype copy of the ND4 gene with an added mitochondrial-targeting sequence—a strategy that had already been shown to correctly direct the protein product of ND4 and other mitochondrial genes to the organelle .
Each of 37 patients received the therapeutic virus via a single injection into the fluid within one eye six to 12 months after the onset @ @ @ @ @ @ @ a sham treatment in the other eye : a surgeon pressed the eye with a blunt cannula to simulate an injection .
“ We thought that , if there was going to be an effect , it would be isolated to that eye and then the other one would be the perfect internal control , ” Yu-Wai-Man tells The Scientist .
“ But as it turns out , that wasn ’ t the case.
” With a slight delay in the sham-treated eye , both eyes started to improve .
By 96 weeks @ @ @ @ @ @ @ had gained visual acuity in both eyes and reported increases in their quality of life .
“ Patients do improve , but , even with the treatment , they still function at a very low level , ” says Byron Lam , an ophthalmologist at the University of Miami who was not involved in the study .
Most of the subjects were still near legal blindness at the end of the study .
To determine how the bilateral effect might be happening , Yu-Wai-Man and colleagues injected the therapeutic virus into one eye @ @ @ @ @ @ @ , they found viral DNA in the noninjected eye and optic nerve .
This raises the possibility that the viral vector supplies the wildtype protein in the untreated eye , but it ’ s not firm proof .
Finding viral DNA in the untreated eye in primates is “ a little short of being definitive because DNA expression alone doesn ’ t prove that you ’ re getting a therapeutic effect .
Detecting DNA doesn ’ t mean there is mRNA expression or protein production , ” says Mark Pennesi , an ophthalmologist @ @ @ @ @ @ @ did not participate in the work .
Previous work has shown that there could “ be transneuronal spread of the vector , but we also need to keep a critical mind and think that there might be other explanations , ” agrees Yu-Wai-Man .
It could be that injecting the vector in one eye leads to some form of localized inflammation that induces mitochondrial biogenesis , thus making the mitochondria work better , he adds .
Another option is that improvement in one eye leads to reorganization in the part of the brain @ @ @ @ @ @ @ which could enhance vision overall .
“ Clearly , further investigations are needed to understand the underlying mechanisms of how the interocular diffusion of viral DNA vector occurs and whether there are other mechanisms by which the optic nerves directly communicate , ” Bin Li , an ophthalmologist at Tongji Hospital in China who was not involved in the study , writes in an email to The Scientist .
Li explains that his group has also reported that material injected in one eye can reach the other optic nerve .
These findings have @ @ @ @ @ @ @ should be performed in the future , he writes .
They ’ ve shown that “ contralateral sham-treated eyes can not serve as ‘ true internal control ’ for clinical studies.
” “ When you read this paper , you get a little excited , and then in some ways , you get a little disappointed , because it does look like there ’ s some kind of positive effect with this treatment—that it does do something more than what would happen with just the natural history of the disease .
Unfortunately , @ @ @ @ @ @ @ that you treat one eye , but then there is improvement in the untreated control eye , ” Pennisi tells The Scientist .
“ The question then really becomes .
.
.
why did you get that result ?
” Along with academic collaborators , Yu-Wai-Man , who consults for GenSight Biologics and Stealth Biotherapeutics , will continue to explore this question as they focus on ongoing clinical trials of this therapeutic .
P. Yu-Wai-Man et al.
, “ Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy , @ @ @ @ @ @ @ 2020 .

ABOVE: Illustration of a mitochondrion. A genetic variant in the mitochondrial genome is responsible for Leber hereditary optic neuropathy.
© ISTOCK.COM, TUSSIK1
I
n a Phase 3 gene therapy trial intended to improve vision among patients with Leber hereditary optic neuropathy, recipients gained somewhat better sight in both eyes even though only one was treated. The results and an investigation into possible explanations for the findings were published December 9 in Science Translational Medicine.
The paper “has very strong clinical implications that a single injection maybe is enough for bilateral effects,” says Thomas Corydon, who studies ocular gene therapy at Aarhaus University in Denmark and was not involved in the work.
The onset of Leber hereditary optic neuropathy (LHON) is sudden. Patients—usually young men—start losing vision at the center of one eye. Within months, the other eye follows, leaving them legally blind. The disease is caused by a point mutation in the mitochondrial genome that leads to dysfunction and death of retinal ganglion cells, the axons of which make up the optic nerve. About 70 percent of patients have the same mutation, known as MT-ND4.
“If you're going to start somewhere, it makes sense to tackle this variant,” says Patrick Yu-Wai-Man, an ophthalmologist at the University of Cambridge in the United Kingdom. He and his collaborators, including teams from GenSight Biologics and a group led by University of Pittsburg Medical Center ophthalmologist José-Alain Sahel, as well as other groups, previously showed that the point mutation could be corrected in animal models and in cell culture using gene therapy.
It’s difficult to get genetic material into the mitochondrial genome because mitochondria have two membranes, an outer and inner membrane, Yu-Wai-Man explains. In the clinical trial, he, Sahel, and colleagues overcame this hurdle by injecting an AAV vector containing a wildtype copy of the ND4 gene with an added mitochondrial-targeting sequence—a strategy that had already been shown to correctly direct the protein product of ND4 and other mitochondrial genes to the organelle.
Each of 37 patients received the therapeutic virus via a single injection into the vitreous fluid within one eye six to 12 months after the onset of vision loss. They also got a sham treatment in the other eye: a surgeon pressed the eye with a blunt cannula to simulate an injection.
“We thought that, if there was going to be an effect, it would be isolated to that eye and then the other one would be the perfect internal control,” Yu-Wai-Man tells The Scientist. “But as it turns out, that wasn’t the case.”
With a slight delay in the sham-treated eye, both eyes started to improve. By 96 weeks after treatment, 29 of the patients had gained visual acuity in both eyes and reported increases in their quality of life.
“Patients do improve, but, even with the treatment, they still function at a very low level,” says Byron Lam, an ophthalmologist at the University of Miami who was not involved in the study. Most of the subjects were still near legal blindness at the end of the study.
To determine how the bilateral effect might be happening, Yu-Wai-Man and colleagues injected the therapeutic virus into one eye of three monkeys. Three months later, they found viral DNA in the noninjected eye and optic nerve. This raises the possibility that the viral vector supplies the wildtype protein in the untreated eye, but it’s not firm proof.
Finding viral DNA in the untreated eye in primates is “a little short of being definitive because DNA expression alone doesn’t prove that you’re getting a therapeutic effect. Detecting DNA doesn’t mean there is mRNA expression or protein production,” says Mark Pennesi, an ophthalmologist at Oregon Health & Science University who did not participate in the work.
Previous work has shown that there could “be transneuronal spread of the vector, but we also need to keep a critical mind and think that there might be other explanations,” agrees Yu-Wai-Man. It could be that injecting the vector in one eye leads to some form of localized inflammation that induces mitochondrial biogenesis, thus making the mitochondria work better, he adds. Another option is that improvement in one eye leads to reorganization in the part of the brain that interprets signals from the eye, which could enhance vision overall.
“Clearly, further investigations are needed to understand the underlying mechanisms of how the interocular diffusion of viral DNA vector occurs and whether there are other mechanisms by which the optic nerves directly communicate,” Bin Li, an ophthalmologist at Tongji Hospital in China who was not involved in the study, writes in an email to The Scientist. Li explains that his group has also reported that material injected in one eye can reach the other optic nerve.
These findings have implications for how this type of research should be performed in the future, he writes. They’ve shown that “contralateral sham-treated eyes cannot serve as ‘true internal control’ for clinical studies.”
“When you read this paper, you get a little excited, and then in some ways, you get a little disappointed, because it does look like there’s some kind of positive effect with this treatment—that it does do something more than what would happen with just the natural history of the disease. Unfortunately, the results are confounded by the fact that you treat one eye, but then there is improvement in the untreated control eye,” Pennisi tells The Scientist. “The question then really becomes . . . why did you get that result?”
Along with academic collaborators, Yu-Wai-Man, who consults for GenSight Biologics, will continue to explore this question as they focus on ongoing clinical trials of this therapeutic.
P. Yu-Wai-Man et al., “Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy,” Science Translational Medicine, doi:10.1126/scitranslmed.aaz7423, 2020.
Correction (December 14): The story has been updated to remove mention of a company that was not involved in the work and to specify which fluid compartment in the eye was injected. The Scientist regrets the error.


thescientist--2020-12-11--The Scientist?'s LabTalk - Episode 4???

The Scientist?'s LabTalk - Episode 4???

Welcome to The Scientist ’ s LabTalk , a special edition podcast produced by The Scientist ’ s Creative Services @ @ @ @ @ at the leading edge of innovative research .
In this episode , Niki Spahich from @ @ @ @ @ Services team spoke with Josh Snow , Director of Business Development and Marketing Strategy at @ @ @ @ @ past , present , and future of gene therapy , with a focus on how @ @ @ @ @ therapies to clinical trials and the market , and the costs involved .
This episode @ @ @ @ @ Mirus Bio .
Mirus Bio pioneered scientific breakthroughs in non-viral gene delivery and continues to @ @ @ @ @ Now as a global leader in transfection technology , Mirus Bio provides life scientists with @ @ @ @ @ gene expression , biotherapeutic protein production , virus manufacturing and genome editing .

Welcome to The Scientist’s LabTalk, a special edition podcast produced by The Scientist’s Creative Services Team where we explore topics at the leading edge of innovative research.
In this episode, Niki Spahich from The Scientist’s Creative Services team spoke with Josh Snow, Director of Business Development and Marketing Strategy at Mirus Bio, about the past, present, and future of gene therapy, with a focus on how researchers can transition their successful therapies to clinical trials and the market, and the costs involved.
This episode is brought to you by Mirus Bio. Mirus Bio pioneered scientific breakthroughs in non-viral gene delivery and continues to produce world-class transfection reagents. Now as a global leader in transfection technology, Mirus Bio provides life scientists with the most advanced tools for gene expression, biotherapeutic protein production, virus manufacturing and genome editing.


thescientist--2020-12-12--Previously Unknown Beaked Whale Species Spotted off Mexico

ABOVE : Two of three whales that belong to a suspected new species swim alongside a research vessel off the coast of Mexico ’ s San Benito Islands .
US NAVY Astrange noise recorded in 2018 in the depths of the Pacific Ocean near Mexico ’ s San Benito Islands may belong to a species of beaked whale that hasn ’ t been documented before , according to a team of scientists working with the Sea Shepherd Conservation Society .
“ We saw something new .
Something that was not expected in this area , something that doesn ’ t @ @ @ @ @ @ @ anything that is known to exist , ” National Oceanic and Atmospheric Administration senior scientist Jay Barlow , who was a member of the team that discovered the whales , says in a statement released by Sea Shepherd on December 8 .
Beaked whales produce loud echolocation clicks to navigate and forage , but the clicks that the team heard had an unusual acoustic profile : they peaked at a different frequency and had a distinctive upsweep , Elizabeth Henderson , a Naval Information Warfare Center Pacific bioacoustics scientist and another scientist on @ @ @ @ @ @ @ Henderson , Barlow , and their colleagues set out on a cruise on November 17 to see if the 2018 sounds were linked to the elusive Perrin ’ s beaked whale ( Mesoplodon perrini ) , which was first described in 2002 and has only been found stranded and dead on the coastline .
Not only did the researchers find the creatures that made the noise , but they stumbled across three of them , all alive .
See “ Clues Point to Climate Change as a Culprit in Gray Whale Deaths.
” @ @ @ @ @ @ @ the Perrin ’ s beaked whale .
For one , the whales ’ teeth were farther back in the mouth , they had a darker coloration band from their eyes to top of their head , and a light streak from their stomachs to midway up their bodies .
“ The fact that they were looking for a very rare whale , and that they happen to find something completely different , is remarkable and wonderful , and just the joy of doing science , ” Andrew Read , a marine biologist at @ @ @ @ @ @ @ the sighting , tells Reuters .
“ That ’ s what we all live for.
” Based on her observations , Henderson says it appears that these whales belong to the Mesoplodon genus and may be closely related to the Perrin ’ s and Blainville ’ s beaked whales .
The researchers tried to collect skin cell samples from the surrounding water to analyze the whales ’ DNA , which would confirm if the whales are , indeed , a novel species , she says .
“ This is pretty significant , ” @ @ @ @ @ @ @ other new species of whale that have been described in the last 20 years have been whales that were already known to exist and were already seen , but new evidence came to light that made a determination that split them from where they were already classified.
” In this case , it appears that the whales had not even been observed by scientists before .
Currently , there are 23 known beaked whale species , and Barlow is “ cautiously optimistic ” that there will soon be 24 .
“ It is @ @ @ @ @ @ @ a Clydesdale horse .
Imagine something that big in the terrestrial realm going undiscovered , ” Barlow tells Reuters .

ABOVE: Two of three whales that belong to a suspected new species swim alongside a research vessel off the coast of Mexico’s San Benito Islands.
US NAVY
Astrange noise recorded in 2018 in the depths of the Pacific Ocean near Mexico’s San Benito Islands may belong to a species of beaked whale that hasn’t been documented before, according to a team of scientists working with the Sea Shepherd Conservation Society.
“We saw something new. Something that was not expected in this area, something that doesn’t match, either visually or acoustically, anything that is known to exist,” National Oceanic and Atmospheric Administration senior scientist Jay Barlow, who was a member of the team that discovered the whales, says in a statement released by Sea Shepherd on December 8.
Beaked whales produce loud echolocation clicks to navigate and forage, but the clicks that the team heard had an unusual acoustic profile: they peaked at a different frequency and had a distinctive upsweep, Elizabeth Henderson, a Naval Information Warfare Center Pacific bioacoustics scientist and another scientist on the team, tells The Scientist.
Henderson, Barlow, and their colleagues set out on a cruise on November 17 to see if the 2018 sounds were linked to the elusive Perrin’s beaked whale (Mesoplodon perrini), which was first described in 2002 and has only been found stranded and dead on the coastline. Not only did the researchers find the creatures that made the noise, but they stumbled across three of them, all alive.
See “Clues Point to Climate Change as a Culprit in Gray Whale Deaths.”
The whales had distinct physical characteristics from the Perrin’s beaked whale. For one, the whales’ teeth were farther back in the mouth, they had a darker coloration band from their eyes to top of their head, and a light streak from their stomachs to midway up their bodies.
“The fact that they were looking for a very rare whale, and that they happen to find something completely different, is remarkable and wonderful, and just the joy of doing science,” Andrew Read, a marine biologist at Duke University who was not involved with the sighting, tells Reuters. “That’s what we all live for.”
Based on her observations, Henderson says it appears that these whales belong to the Mesoplodon genus and may be closely related to the Perrin’s and Blainville’s beaked whales. The researchers tried to collect skin cell samples from the surrounding water to analyze the whales’ DNA, which would confirm if the whales are, indeed, a novel species, she says.
“This is pretty significant,” Henderson tells The Scientist. “Most other new species of whale that have been described in the last 20 years have been whales that were already known to exist and were already seen, but new evidence came to light that made a determination that split them from where they were already classified.” In this case, it appears that the whales had not even been observed by scientists before.
Currently, there are 23 known beaked whale species, and Barlow is “cautiously optimistic” that there will soon be 24. “It is a huge animal, the weight of a Clydesdale horse. Imagine something that big in the terrestrial realm going undiscovered,” Barlow tells Reuters.


thescientist--2020-12-14--Key Genes Related to Severe COVID-19 Infection Identified

More than a year after the first cases of COVID-19 were detected , researchers are still trying to understand why some people infected with the virus become critically ill , while others have little to no symptoms .
Scientists have turned to look at the genes of patients with severe COVID-19 to understand if their bodies mount an immune defense differently than healthy patients do .
A genome-wide association study published in Nature on December 11 finds that variants of five key genes responsible for antiviral immunity and lung inflammation are associated with severe COVID-19 .
The findings offer potential @ @ @ @ @ @ @ treatment .
“ Our results immediately highlight which drugs should be at the top of the list for clinical testing , ” Kenneth Baillie , a consultant in critical care medicine and a senior research fellow at the University of Edinburgh , tells Reuters .
Baillie and his colleagues analyzed the DNA of 2,244 patients across 208 UK intensive care units and compared it to matched controls who did not have a positive COVID-19 PCR test on file .
They identified eight loci where variants were more common among the intensive care patients @ @ @ @ @ @ @ linked to the immune system—IFNAR2 , TYK2 , OAS1 , DPP9 , and CCR2 .
An analysis looking into the relationship between the activity of certain genes and severe COVID-19 pointed to a lower expression of IFNAR2 , a gene that encodes a building block of a receptor for interferons , which act as emergency flares to warn the immune system of an intruder and have been a target for researchers hoping to develop a COVID-19 treatment .
However , administering interferon to hospitalized COVID-19 patients did not reduce mortality , according to @ @ @ @ @ @ @ month .
The researchers also homed in on a possible link between severe COVID-19 and higher expression levels of TYK2 and CCR2 , which encode proteins used in cytokine signaling , which drives inflammation and can lead to lung injury .
The anti-inflammatory drug baricitinib , typically used to treat rheumatoid arthritis , inhibits the protein encoded by the TYK2 gene and has shown promising results in treating COVID-19 when paired with remdesivir , a broad spectrum antiviral that has shown limited effectiveness against the virus by itself , according to a study @ @ @ @ @ @ @ Journal of Medicine .
See “ AI Is Screening Billions of Molecules for Coronavirus Treatments ” While the Nature study may offer clues for the genetic underpinnings of severe COVID-19 infection , finding an effective treatment in humans may still be years away .
“ There is no guarantee that when a gene is found , targeting that gene will result in therapeutic efficacy , ” Tom Hemming Karlsen , a physician at the University of Oslo who did not participate in the new work , tells The Washington Post .
“ What @ @ @ @ @ @ @ they help us find very specific starting points ” for further investigation .
Sara Clohisey , a research fellow at the University of Edinburgh and a coauthor of the Nature study , notes that her findings don ’ t suggest a direct causal relationship between these gene variants and COVID-19 disease severity .
“ A chunk of the answer is in our genes , ” but “ it ’ s unlikely that a single element is fully responsible for the development of severe COVID-19 , ” she tells the Post .
“ It @ @ @ @ @ @ @ combination of factors , ” which may include genetics as well as age , obesity , gender , and other characteristics .

ABOVE: © ISTOCK.COM,
NOVIELYSA
More than a year after the first cases of COVID-19 were detected, researchers are still trying to understand why some people infected with the virus become critically ill, while others have little to no symptoms. Scientists have turned to look at the genes of patients with severe COVID-19 to understand if their bodies mount an immune defense differently than healthy patients do. A genome-wide association study published in Nature on December 11 finds that variants of five key genes responsible for antiviral immunity and lung inflammation are associated with severe COVID-19.
The findings offer potential therapeutic targets to create an effective COVID-19 treatment. “Our results immediately highlight which drugs should be at the top of the list for clinical testing,” Kenneth Baillie, a consultant in critical care medicine and a senior research fellow at the University of Edinburgh, tells Reuters.
Baillie and his colleagues analyzed the DNA of 2,244 patients across 208 UK intensive care units and compared it to matched controls who did not have a positive COVID-19 PCR test on file. They identified eight loci where variants were more common among the intensive care patients, of which five were in genes linked to the immune system—IFNAR2, TYK2, OAS1, DPP9, and CCR2.
An analysis looking into the relationship between the activity of certain genes and severe COVID-19 pointed to a lower expression of IFNAR2, a gene that encodes a building block of a receptor for interferons, which act as emergency flares to warn the immune system of an intruder and have been a target for researchers hoping to develop a COVID-19 treatment. However, administering interferon to hospitalized COVID-19 patients did not reduce mortality, according to a large clinical trial published earlier this month.
The researchers also homed in on a possible link between severe COVID-19 and higher expression levels of TYK2 and CCR2, which encode proteins used in cytokine signaling, which drives inflammation and can lead to lung injury. The anti-inflammatory drug baricitinib, typically used to treat rheumatoid arthritis, inhibits the protein encoded by the TYK2 gene and has shown promising results in treating COVID-19 when paired with remdesivir, a broad spectrum antiviral that has shown limited effectiveness against the virus by itself, according to a study published December 11 in The New England Journal of Medicine.
See “AI Is Screening Billions of Molecules for Coronavirus Treatments”
While the Nature study may offer clues for the genetic underpinnings of severe COVID-19 infection, finding an effective treatment in humans may still be years away. “There is no guarantee that when a gene is found, targeting that gene will result in therapeutic efficacy,” Tom Hemming Karlsen, a physician at the University of Oslo who did not participate in the new work, tells The Washington Post. “What genetics studies like this then do is they help us find very specific starting points” for further investigation.
The authors' investigation indicated that there is a causal role for IFNAR2 and TYK2. Sara Clohisey, a research fellow at the University of Edinburgh and a coauthor of the Nature study, notes that there are likely many other factors beyond these gene variants that contribute to COVID-19 disease severity.
“A chunk of the answer is in our genes,” but “it’s unlikely that a single element is fully responsible for the development of severe COVID-19,” she tells the Post. “It’s more likely to be a combination of factors,” which may include genetics as well as age, obesity, gender, and other characteristics.
Correction (December 15): A previous version of this article misinterpreted Sara Clohisey's comments about the causality of her findings. The Scientist regrets the error.


thescientist--2020-12-14--Conference Linked to as Many as 300,000 COVID-19 Cases: Study

The United States had its first coronavirus superspreader event during a two-day conference in Boston organized by the biotech company Biogen in February .
Genetic testing has revealed that what began with 99 people who became infected with SARS-CoV-2 at the event , another 205,000–300,000 cases subsequently resulted as the attendees returned home to 29 states and several other countries , carrying the virus with them , according to a study published in Science on December 10 .
A national database of SARS-CoV-2 genomes and contact tracing has allowed the authors to track which strains were being transmitted .
As @ @ @ @ @ @ @ of the pandemic attributed to the conference is roughly 1.6 percent of all US COVID-19 cases .
By performing genetic analyses from 28 of the infected conference-goers , researchers were able to identify the viral strain that circulated among them and that then spread around the country .
They found that the strain from the conference hadn ’ t been seen in the US before that , only in France .
The conference was held February 26 and 27 , weeks before any state declared stay-at-home orders or other measures to curb COVID-19 @ @ @ @ @ @ @ of Public Health , there were only three presumptive cases in the first week of March and the state ’ s Public Health Commissioner Monica Bharel said at the time that there was low risk in Massachusetts .
“ It ’ s a cautionary tale , ” Bronwyn MacInnis , a genomic epidemiologist at the Broad Institute of Harvard and MIT and a coauthor of the paper , tells The New York Times .
“ When we hear these stories of clusters where 20 or 50 or 100 were affected , that does @ @ @ @ @ @ @ Soon after the cluster of cases was tied to the event in the spring , Biogen partnered with the Broad Institute to create a biobank to learn as much as possible about COVID-19 through blood samples from Biogen employees and their close contacts .
The company has maintained a presence in COVID-19 research .
See “ Biogen Uses its Own Superspreader Event to Aid COVID-19 Research ” “ Tremendous progress has been made since the start of the pandemic to gain a better understanding of this novel virus and its transmission , develop @ @ @ @ @ @ @ , ” reads a Biogen statement to the Globe , following the publication of the study .
“ As a company rooted in science , we understand the value of the data that came from the first wave of the pandemic in the Boston area and we hope that information gleaned from these data will help continue to drive a better understanding of the transmission of this virus and efforts to address it.
” The authors expressed in various news reports that while the strain is unique , it isn ’ t more @ @ @ @ @ @ @ that allow these super-spreading events to occur are very much still with us and will continue to be with us for a long time , ” lead author Jacob Lemieux of the Broad Institute tells the Times , warning about the upcoming holidays .
“ Maintain social distancing , wear masks whenever possible and avoid indoor gatherings .
”

ABOVE: © ISTOCK.COM,
METAMORWORKS
The United States had its first coronavirus superspreader event during a two-day conference in Boston organized by the biotech company Biogen in February. Genetic testing has revealed that what began with 99 people who became infected with SARS-CoV-2 at the event, another 205,000–300,000 cases subsequently resulted as the attendees returned home to 29 states and several other countries, carrying the virus with them, according to a study published in Science on December 10.
A national database of SARS-CoV-2 genomes and contact tracing has allowed the authors to track which strains were being transmitted. As The Boston Globe reports, the proportion of the pandemic attributed to the conference is roughly 1.6 percent of all US COVID-19 cases.
By performing genetic analyses from 28 of the infected conference-goers, researchers were able to identify the viral strain that circulated among them and that then spread around the country. They found that the strain from the conference hadn’t been seen in the US before that, only in France.
The conference was held February 26 and 27, weeks before any state declared stay-at-home orders or other measures to curb COVID-19 transmission. According to the Massachusetts Department of Public Health, there were only three presumptive cases in the first week of March and the state’s Public Health Commissioner Monica Bharel said at the time that there was low risk in Massachusetts.
“It’s a cautionary tale,” Bronwyn MacInnis, a genomic epidemiologist at the Broad Institute of Harvard and MIT and a coauthor of the paper, tells The New York Times. “When we hear these stories of clusters where 20 or 50 or 100 were affected, that does not account for what happens after.”
Soon after the cluster of cases was tied to the event in the spring, Biogen partnered with the Broad Institute to create a biobank to learn as much as possible about COVID-19 through blood samples from Biogen employees and their close contacts. The company has maintained a presence in COVID-19 research.
“Tremendous progress has been made since the start of the pandemic to gain a better understanding of this novel virus and its transmission, develop vaccines, and investigate potential treatment options,” reads a Biogen statement to the Globe, following the publication of the study. “As a company rooted in science, we understand the value of the data that came from the first wave of the pandemic in the Boston area and we hope that information gleaned from these data will help continue to drive a better understanding of the transmission of this virus and efforts to address it.”
The authors expressed in various news reports that while the strain is unique, it isn’t more virulent than others.
“The conditions that allow these super-spreading events to occur are very much still with us and will continue to be with us for a long time,” lead author Jacob Lemieux of the Broad Institute tells the Times, warning about the upcoming holidays. “Maintain social distancing, wear masks whenever possible and avoid indoor gatherings.”


thescientist--2020-12-14--Study Estimates 76 Percent of Brazilian City Exposed to SARS-CoV-2

In a study published in Science December 8 , a group of researchers estimate that 76 percent of the population of Manaus , the first Brazilian city to be hard hit by the coronavirus pandemic , could have been infected with the SARS-CoV-2 virus so far , based on antibodies present in samples from blood banks .
The report also estimates that in São Paulo , Brazil ’ s largest city , that percentage is much lower , accounting for 29 percent of the population .
According to the paper , these results highlight the failure of Manaus to control @ @ @ @ @ @ @ findings are based on the analysis of samples from donor blood centers .
Because Brazilian law establishes that blood banks should keep samples for six months , the researchers were able to go back in time and trace the unravelling of the pandemic between February and October .
In the case of Manaus , they observed that the proportion of blood donors with antibodies against SARS-CoV-2 was around 5 percent in April , but increased steeply to almost 40 percent in May .
After adjusting the results for age and sex , for @ @ @ @ @ @ @ for the decay in antibodies in the samples , the researchers extrapolate that by June , 66.2 percent of the population had been infected , a figure that rose to 76 percent by October .
An average of around 900 to 1,000 samples were analyzed for each month and city .
“ The sixty-six percent figure sets the theoretical threshold for herd immunity , but cases are still increasing in Manaus , ” says Ester Sabino , an immunologist at the University of São Paulo and lead author of the study .
An @ @ @ @ @ @ @ to a preprint repository in September , stated that the high presence of antibodies against SARS-CoV-2 in the population meant that Manaus would have achieved herd immunity .
The manuscript was met with fierce backlash by part of the medical and scientific community , who considered that such a claim could make the population take fewer precautions and could be used by politicians to lift restrictions .
Just a few days after the preprint came out , the city experienced a second wave of cases after a period of stability .
While both @ @ @ @ @ @ @ be causally connected , the paper may have contributed to a delay in the response and a failure to acknowledge the severity of the situation , according to news outlet Amazonia Real .
To address this criticism , the peer-reviewed version of the study has downplayed the statements referring to herd immunity , noting that “ prior infection might not confer long-lasting immunity.
” “ It looked like we had said that by reaching herd immunity the epidemic was over , but that was not what we meant , so we rewrote the @ @ @ @ @ @ @ ” says Sabino .
Located in the heart of the Amazon forest , hundreds of miles away from the country ’ s economic and political centers , Manaus is an industrial city with a population of more than 2 million .
Since the pandemic started , the city has had more than 73,000 confirmed positive cases of COVID-19 and some 3,000 deaths , according to official figures .
However , experts agree that the real figures are probably much higher , as few tests are performed .
The shocking photographs of mass graves @ @ @ @ @ @ @ in April were some of the earliest graphic testimonies of the severity of the pandemic .
According to a study published in a Brazilian journal , the number of total deaths in Manaus in April was more than 4.5 times higher than in previous years .
All the experts who spoke with The Scientist agree that the main limitation of this new study is that blood bank donors are not representative of the total population .
The researchers adjusted for some of the demographic skew in the sample by comparing it to the @ @ @ @ @ @ @ far from perfect .
Jesem Orellana , an epidemiologist from Manaus who works at the Fundação Oswaldo Cruz , a public research institution , notes the prospect of a free COVID-19 test upon donating blood may have prompted specific groups of people to contribute .
“ Many people may have donated blood to know their serological status , especially those who suspected they had been infected and with less financial resources , ” Orellana says .
He adds that the blood center even partnered with Uber to offer a discount to donors heading @ @ @ @ @ @ @ might have influenced the outcome of the study .
See “ Researchers in Brazil Struggle to Get Solid COVID-19 Death Counts ” Another challenge for the researchers was dealing with antibody waning .
The kit used in the study was able to detect IgG antibodies against SARS-CoV-2 fairly well if the patient had been infected recently .
But as weeks passed , the signal became weaker and more difficult to identify , according to the study .
To overcome this , the authors developed a mathematical model to correct for cases that were @ @ @ @ @ @ @ signal , but overlooked by the assay .
This proved especially important for the samples from Manaus , as most infections appear to have happened in the early days of the pandemic , around April .
People who were infected in April or May , but donated in September or October , had by then experienced a decay in the number of antibodies , which made it difficult for the researchers to identify these cases as positive .
In São Paulo , where the infection curve was more contained , this correction wasn @ @ @ @ @ @ @ , according to the authors , as the antibody waning from old infections was compensated by new infections .
In Manaus , the study has been received with skepticism by the scientific and medical communities .
The extensive media coverage that the early September version of the study received , filled with claims that the city had reached herd immunity , made it increasingly difficult for health officials to convey the need for keeping restrictions and social distance measures .
Political decisions in the region , such as reopening schools , were influenced @ @ @ @ @ @ @ magazine Época .
So while the new version of the study puts less weight on herd immunity , many still worry that the paper may do more harm than good .
Cristiano Fernandes , the technical director of the Fundação Vigilância e Saúde do Amazonas , a department of the State Health Secretariat that has been at the frontline of the pandemic response , criticizes the paper ’ s repeated use of the term “ unmitigated ” to refer to how the pandemic unfolded in the city .
“ Saying that Manaus did @ @ @ @ @ @ @ the disease is just not true .
To make such a claim was inelegant and unnecessary , to say the least , ” says Fernandes , who notes that there might have been other factors that contributed to the severity of the pandemic in Manaus .
One of the factors pointed out by Fernandes is the existence of at least eight different strains of the new coronavirus circulating in the state where Manaus is located .
This suggests that the virus arrived through multiple paths , which could have amplified the development of @ @ @ @ @ @ @ to several researchers who spoke with The Scientist , the city ’ s precarious health system may have also played a role in the pandemic response .
Despite its size and wealth , Manaus has few intensive care unit beds , which serve not only the city , but the whole state of Amazonas , an area which is approximately 3.5 times bigger than California .
“ Manaus absorbed a high load [ of patients ] from the municipalities in the interior [ of the state ] , where there is no appropriate @ @ @ @ @ @ @ , an epidemiologist at the Fundação Oswaldo Cruz who was critical of the new study .
“ There are still many questions and few reliable answers.
” A previous study using serological household surveys estimated that in June , 14 percent of the population had been infected—much lower than the 66.2 percent figure found in this new study for that month .
While the household survey also has some limitations , the disparity between the studies calls for caution in interpreting the results .
Microbiologist Natalia Pasternak , the director of the Instituto @ @ @ @ @ @ @ that promotes scientific integrity and has been monitoring the pandemic in Brazil since its early days , describes the study in a positive light .
However , she warns that the 76 percent figure should be seen as an estimate .
With COVID-19 cases continuing to be very high in Manaus , and nearly all intensive care unit beds currently occupied , there is clearly a substantial amount of the population still vulnerable .
“ I think we need to stress that herd immunity will only be achieved through vaccines , ” says @ @ @ @ @ @ @ “ Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic , ” Science , doi:10.1126/science.abe9728 , 2020 .

ABOVE: © ISTOCK.COM, DANIEL FIGUERIEDO
In a study published in Science December 8, a group of researchers estimate that 76 percent of the population of Manaus, the first Brazilian city to be hard hit by the coronavirus pandemic, could have been infected with the SARS-CoV-2 virus so far, based on antibodies present in samples from blood banks. The report also estimates that in São Paulo, Brazil’s largest city, that percentage is much lower, accounting for 29 percent of the population. According to the paper, these results highlight the failure of Manaus to control the spread of the virus.
The findings are based on the analysis of samples from donor blood centers. Because Brazilian law establishes that blood banks should keep samples for six months, the researchers were able to go back in time and trace the unravelling of the pandemic between February and October. In the case of Manaus, they observed that the proportion of blood donors with antibodies against SARS-CoV-2 was around 5 percent in April, but increased steeply to almost 40 percent in May. After adjusting the results for age and sex, for the sensitivity of the test, and for the decay in antibodies in the samples, the researchers extrapolate that by June, 66.2 percent of the population had been infected, a figure that rose to 76 percent by October. An average of around 900 to 1,000 samples were analyzed for each month and city.
“The sixty-six percent figure sets the theoretical threshold for herd immunity, but cases are still increasing in Manaus,” says Ester Sabino, an immunologist at the University of São Paulo and lead author of the study.
An early version of the paper, uploaded to a preprint repository in September, stated that the high presence of antibodies against SARS-CoV-2 in the population meant that Manaus would have achieved herd immunity. The manuscript was met with fierce backlash by part of the medical and scientific community, who considered that such a claim could make the population take fewer precautions and could be used by politicians to lift restrictions. Just a few days after the preprint came out, the city experienced a second wave of cases after a period of stability. While both events happened too close in time to be causally connected, the paper may have contributed to a delay in the response and a failure to acknowledge the severity of the situation, according to news outlet Amazonia Real.
With COVID-19 cases continuing to be very high in Manaus, and nearly all intensive care unit beds currently occupied, there is clearly a substantial amount of the population still vulnerable.
To address this criticism, the peer-reviewed version of the study has downplayed the statements referring to herd immunity, noting that “prior infection might not confer long-lasting immunity.”
“It looked like we had said that by reaching herd immunity the epidemic was over, but that was not what we meant, so we rewrote the text to try to improve that,” says Sabino.
Located in the heart of the Amazon forest, hundreds of miles away from the country’s economic and political centers, Manaus is an industrial city with a population of more than 2 million.
Since the pandemic started, the city has had more than 73,000 confirmed positive cases of COVID-19 and some 3,000 deaths, according to official figures. However, experts agree that the real figures are probably much higher, as few tests are performed. The shocking photographs of mass graves in the city’s cemetery back in April were some of the earliest graphic testimonies of the severity of the pandemic. According to a study published in a Brazilian journal, the number of total deaths in Manaus in April was more than 4.5 times higher than in previous years.
Extrapolation from blood donors
All the experts who spoke with The Scientist agree that the main limitation of this new study is that blood bank donors are not representative of the total population. The researchers adjusted for some of the demographic skew in the sample by comparing it to the population census, but the approach is far from perfect.
Jesem Orellana, an epidemiologist from Manaus who works at the Fundação Oswaldo Cruz, a public research institution, notes the prospect of a free COVID-19 test upon donating blood may have prompted specific groups of people to contribute.
“Many people may have donated blood to know their serological status, especially those who suspected they had been infected and with less financial resources,” Orellana says. He adds that the blood center even partnered with Uber to offer a discount to donors heading to the facility. All of this might have influenced the outcome of the study.
Another challenge for the researchers was dealing with antibody waning. The kit used in the study was able to detect IgG antibodies against SARS-CoV-2 fairly well if the patient had been infected recently. But as weeks passed, the signal became weaker and more difficult to identify, according to the study.
To overcome this, the authors developed a mathematical model to correct for cases that were likely positive based on a weak antibody signal, but overlooked by the assay. This proved especially important for the samples from Manaus, as most infections appear to have happened in the early days of the pandemic, around April. People who were infected in April or May, but donated in September or October, had by then experienced a decay in the number of antibodies, which made it difficult for the researchers to identify these cases as positive.
In São Paulo, where the infection curve was more contained, this correction wasn’t so relevant for the calculation, according to the authors, as the antibody waning from old infections was compensated by new infections.
The pandemic in Manaus
In Manaus, the study has been received with skepticism by the scientific and medical communities. The extensive media coverage that the early September version of the study received, filled with claims that the city had reached herd immunity, made it increasingly difficult for health officials to convey the need for keeping restrictions and social distance measures. Political decisions in the region, such as reopening schools, were influenced by the study, according to the magazine Época. So while the new version of the study puts less weight on herd immunity, many still worry that the paper may do more harm than good.
Cristiano Fernandes, the technical director of the Fundação Vigilância e Saúde do Amazonas, a department of the State Health Secretariat that has been at the frontline of the pandemic response, criticizes the paper’s repeated use of the term “unmitigated” to refer to how the pandemic unfolded in the city.
“Saying that Manaus did not have a mitigation plan to restrain the disease is just not true. To make such a claim was inelegant and unnecessary, to say the least,” says Fernandes, who notes that there might have been other factors that contributed to the severity of the pandemic in Manaus.
One of the factors pointed out by Fernandes is the existence of at least eight different strains of the new coronavirus circulating in the state where Manaus is located. This suggests that the virus arrived through multiple paths, which could have amplified the development of the pandemic in the city.
According to several researchers who spoke with The Scientist, the city’s precarious health system may have also played a role in the pandemic response. Despite its size and wealth, Manaus has few intensive care unit beds, which serve not only the city, but the whole state of Amazonas, an area which is approximately 3.5 times bigger than California.
“Manaus absorbed a high load [of patients] from the municipalities in the interior [of the state], where there is no appropriate health infrastructure,” says Felipe Naveca, an epidemiologist at the Fundação Oswaldo Cruz who was critical of the new study. “There are still many questions and few reliable answers.”
A previous study using serological household surveys estimated that in June, 14 percent of the population had been infected—much lower than the 66.2 percent figure found in this new study for that month. While the household survey also has some limitations, the disparity between the studies calls for caution in interpreting the results.
Microbiologist Natalia Pasternak, the director of the Instituto Questão de Ciencia, a private organization that promotes scientific integrity and has been monitoring the pandemic in Brazil since its early days, describes the study in a positive light. However, she warns that the 76 percent figure should be seen as an estimate. With COVID-19 cases continuing to be very high in Manaus, and nearly all intensive care unit beds currently occupied, there is clearly a substantial amount of the population still vulnerable.
“I think we need to stress that herd immunity will only be achieved through vaccines,” says Pasternak.
L.F. Buss et al, “Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic,” Science, doi:10.1126/science.abe9728, 2020.


thescientist--2020-12-15--ATCC Introduces New Product Segment with Launch of SARS-CoV-2 External Control Kit

ATCC , the world ’ s premier biological materials management and standards organization , today announced the introduction of its new SARS-CoV-2 External Control Kit for clinical laboratories and test manufacturers .
The ready-to-run kit provides controls in the rapidly changing COVID-19 testing landscape as a workflow-optimized kit with complete genome coverage that ’ s widely compatible with most commercial and laboratory-developed tests .
Federal regulation requires that clinical laboratories assess the performance of their testing applications .
This new ATCC kit is a practical , kitted solution clinical laboratories can use to meet this requirement .
Validated , convenient @ @ @ @ @ @ @ universal , full-process positive control ( a heat-inactivated virus ) and negative control ( human cell line ) that allow clinical laboratories to easily and accurately verify and assess the quality of their molecular diagnostic assays .
“ This is the very first diagnostic quality control product that ATCC has brought to market , ” said Raymond H. Cypess , DVM , Ph.D. , Chairman and CEO of ATCC .
“ It ’ s a logical next step for ATCC as it leverages our deep expertise in materials validation and standards .
This @ @ @ @ @ @ @ their regulatory obligations , and test manufacturers validate their products so that both may continue to play a critical role as part of the global response to this ongoing pandemic.
” The SARS-CoV-2 External Control Kit is compatible with most molecular diagnostic tests being used today .
This broad compatibility is critical as surveys from the Association for Molecular Pathology have shown that supply shortages and other factors have led most clinical laboratories to perform COVID-19 diagnostic testing using more than one commercially available and/or laboratory-developed test .
The kit includes positive and @ @ @ @ @ @ @ determine the performance quality of the lab ’ s entire testing workflow , including sample extraction and target amplification , regardless of which molecular diagnostic test is being used .
“ The positive and negative controls are , as usual , high-quality products from ATCC .
These provide reliable and safe process controls for use across the wide range of settings where SARS-CoV-2 molecular testing will be performed , ” said Jesse J. Waggoner , M.D.
, Assistant Professor , Department of Medicine , at Emory University School of Medicine .
“ In @ @ @ @ @ @ @ at a concentration relevant for clinical diagnostic testing : high enough to provide consistent results , but low enough as to require good test performance for detection.
” The ATCC SARS-CoV-2 External Control Kit combines genome coverage of the entire heat-inactivated , native reference strain of the virus at an optimized concentration and a published genomic sequence so that clinical laboratories and test manufacturers can track the mutation rate of the virus over time and adjust as needed .

ATCC, the world’s premier biological materials management and standards organization, today announced the introduction of its new SARS-CoV-2 External Control Kit for clinical laboratories and test manufacturers. The ready-to-run kit provides controls in the rapidly changing COVID-19 testing landscape as a workflow-optimized kit with complete genome coverage that’s widely compatible with most commercial and laboratory-developed tests.
Federal regulation requires that clinical laboratories assess the performance of their testing applications. This new ATCC kit is a practical, kitted solution clinical laboratories can use to meet this requirement. Validated, convenient, and ready-to-use, it offers a universal, full-process positive control (a heat-inactivated virus) and negative control (human cell line) that allow clinical laboratories to easily and accurately verify and assess the quality of their molecular diagnostic assays.
“This is the very first diagnostic quality control product that ATCC has brought to market,” said Raymond H. Cypess, DVM, Ph.D., Chairman and CEO of ATCC. “It’s a logical next step for ATCC as it leverages our deep expertise in materials validation and standards. This reliable kit can help clinical laboratories meet their regulatory obligations, and test manufacturers validate their products so that both may continue to play a critical role as part of the global response to this ongoing pandemic.”
The SARS-CoV-2 External Control Kit is compatible with most molecular diagnostic tests being used today. This broad compatibility is critical as surveys from the Association for Molecular Pathology have shown that supply shortages and other factors have led most clinical laboratories to perform COVID-19 diagnostic testing using more than one commercially available and/or laboratory-developed test. The kit includes positive and negative controls that can be used to determine the performance quality of the lab’s entire testing workflow, including sample extraction and target amplification, regardless of which molecular diagnostic test is being used.
“The positive and negative controls are, as usual, high-quality products from ATCC. These provide reliable and safe process controls for use across the wide range of settings where SARS-CoV-2 molecular testing will be performed,” said Jesse J. Waggoner, M.D., Assistant Professor, Department of Medicine, at Emory University School of Medicine. “In addition, the positive control is provided at a concentration relevant for clinical diagnostic testing: high enough to provide consistent results, but low enough as to require good test performance for detection.”
The ATCC SARS-CoV-2 External Control Kit combines genome coverage of the entire heat-inactivated, native reference strain of the virus at an optimized concentration and a published genomic sequence so that clinical laboratories and test manufacturers can track the mutation rate of the virus over time and adjust as needed.


thescientist--2020-12-15--New England Biolabs® Introduces NEBNext® Custom RNA Depletion Design Tool and RNA Depletion

New England Biolabs® Introduces NEBNext® Custom RNA Depletion Design Tool and RNA Depletion Core Reagent Set for Customizable RNA Depletion

New England Biolabs ( NEB® ) announced further expansion of its RNA depletion product portfolio with the launch of the NEBNext Custom RNA Depletion Design Tool and NEBNext RNA Depletion Core Reagent Set .
Together , these enable a fully customizable workflow for improved removal of specific RNAs , including abundant RNAs such as ribosomal RNA ( rRNA ) .
This approach can be applied to any sample , including those from less commonly used organisms , and from difficult sample types such as formalin-fixed paraffin embedded ( FFPE ) tissue samples .
`` The removal of abundant RNA is @ @ @ @ @ @ @ , including RNA sequencing '' said Fiona Stewart , Ph.D. , Product Portfolio Manager , Next Generation Sequencing at NEB .
`` However , removing undesirable RNA sequences from atypical samples , which are not compatible with existing RNA depletion kits on the market , is a challenge faced by many researchers .
This problem led us to develop a fully customizable and user-friendly solution that allows scientists to create custom probe sequences which work synergistically with our RNase H-based RNA depletion technology to quickly degrade undesirable RNAs from a broad range of @ @ @ @ @ @ @ Custom RNA Depletion Design Tool allows researchers to input their target RNA sequence to obtain custom probe sequences 40 to 60 bases long .
Probes can then be sourced from their preferred oligo provider and can be used with the NEBNext Custom RNA Depletion Core Reagent Set or as additions to the probe sets in other NEBNext RNA Depletion Kits ( rRNA removal for human , mouse , rat and bacteria samples , and globin mRNA removal ) .
These kits utilize the NEBNext RNase H-based depletion workflow , which is compatible with @ @ @ @ @ @ @ low-quality RNA samples .
The workflow can be completed in two hours , with only 10 minutes of hands-on time .
`` This technology has been superb for eliminating the ribosomal RNA for a range of custom projects , including tracking novel viruses in mosquitoes , longitudinal profiling for astronauts , and host-pathogen interactions in COVID samples , '' said Dr. Christopher Mason , a geneticist and recent user .
`` Any species can now have a rich , in-depth profile created of its complex transcriptome , from non-coding RNAs to RNA modifications @ @ @ @ @ @ @ design sequences for rRNA removal that NEB is providing to the research community has been very useful for us , '' said Vladimir Benes , Head of Genomics Core Facility at the European Molecular Biology Laboratory .
`` This method for customization of RNA depletion has proven valuable for a range of organisms .
Use of custom probes for Xenopus laevis ribosomal RNA worked very well , resulting in complete depletion .
And supplementing the probes in the NEBNext rRNA Depletion Kit ( Bacteria ) with custom probes for the bacillus Eggerthella lenta @ @ @ @ @ @ @ ribosomal RNA . ''

New England Biolabs (NEB®) announced further expansion of its RNA depletion product portfolio with the launch of the NEBNext Custom RNA Depletion Design Tool and NEBNext RNA Depletion Core Reagent Set. Together, these enable a fully customizable workflow for improved removal of specific RNAs, including abundant RNAs such as ribosomal RNA (rRNA). This approach can be applied to any sample, including those from less commonly used organisms, and from difficult sample types such as formalin-fixed paraffin embedded (FFPE) tissue samples.
"The removal of abundant RNA is a critical step for many RNA-based applications, including RNA sequencing" said Fiona Stewart, Ph.D., Product Portfolio Manager, Next Generation Sequencing at NEB. "However, removing undesirable RNA sequences from atypical samples, which are not compatible with existing RNA depletion kits on the market, is a challenge faced by many researchers. This problem led us to develop a fully customizable and user-friendly solution that allows scientists to create custom probe sequences which work synergistically with our RNase H-based RNA depletion technology to quickly degrade undesirable RNAs from a broad range of input amounts."
The free NEBNext Custom RNA Depletion Design Tool allows researchers to input their target RNA sequence to obtain custom probe sequences 40 to 60 bases long. Probes can then be sourced from their preferred oligo provider and can be used with the NEBNext Custom RNA Depletion Core Reagent Set or as additions to the probe sets in other NEBNext RNA Depletion Kits (rRNA removal for human, mouse, rat and bacteria samples, and globin mRNA removal).
These kits utilize the NEBNext RNase H-based depletion workflow, which is compatible with 10 ng – 1 µg of high-and low-quality RNA samples. The workflow can be completed in two hours, with only 10 minutes of hands-on time.
"This technology has been superb for eliminating the ribosomal RNA for a range of custom projects, including tracking novel viruses in mosquitoes, longitudinal profiling for astronauts, and host-pathogen interactions in COVID samples," said Dr. Christopher Mason, a geneticist and recent user. "Any species can now have a rich, in-depth profile created of its complex transcriptome, from non-coding RNAs to RNA modifications."
"The open-access tool to design sequences for rRNA removal that NEB is providing to the research community has been very useful for us," said Vladimir Benes, Head of Genomics Core Facility at the European Molecular Biology Laboratory. "This method for customization of RNA depletion has proven valuable for a range of organisms. Use of custom probes for Xenopus laevis ribosomal RNA worked very well, resulting in complete depletion. And supplementing the probes in the NEBNext rRNA Depletion Kit (Bacteria) with custom probes for the bacillus Eggerthella lenta led to 90% depletion of the ribosomal RNA."


thescientist--2020-12-15--FUJIFILM Irvine Scientific Introduces Sterile Express Media Service

FUJIFILM Irvine Scientific , Inc. , today announced the launch of Sterile Express Media Service ( SEMS ) , for small-scale , rapid production of non-GMP media tested for sterility .
With SEMS , customers can request up to 100L of media , to be rapidly manufactured in a Grade A/ISO 5 sterile environment , and have it shipped within 15 business days pending sterility confirmation .
Contamination in culture media can affect cell characteristics such as growth , metabolism , and morphology , contributing to unreliable or erroneous results .
This can cause delays in the development and scale-up @ @ @ @ @ @ @ enable manufacturers to test the feasibility of formulations using sterile cell culture media before scale-up to more costly GMP manufacturing .
Sterile media provide an extra measure of control and security for valuable cells and streamline the successful development of cell and gene therapies and biopharmaceutical drugs .
Unlike the sterile-filtered and sterile-tested media currently available in the market , SEMS utilizes isolator technology to provide an aseptic manufacturing environment .
SEMS media remain in a Grade A/ISO 5 environment throughout the manufacturing process , reducing the risk of contamination for critical applications @ @ @ @ @ @ @ manufactured using the same qualified raw materials used for GMP manufacturing and are sterility tested according to USP71 and ISO 13408 requirements .
Erik Vaessen , Ph.D. , Executive Director , Life Sciences at FUJIFILM Irvine Scientific commented : “ Until now , there has never been a rapid , non-GMP manufacturing service that delivers sterile cell culture media .
Sterile Express Media Service is a first-of-its-kind offering that enables FUJIFILM Irvine Scientific customers to use sterile media for trials , which may also help reduce costs associated with developing therapies and biopharmaceutical @ @ @ @ @ @ @ testing phase .
We are pleased to offer this innovation to our customers.
” SEMS is part of the FUJIFILM Irvine Scientific group of media services that also include Express Media Service ( EMS ) for small-scale , rapid production of non-GMP media and Media Development and Optimization Services ( MDO ) for the development of custom media .

FUJIFILM Irvine Scientific, Inc., today announced the launch of Sterile Express Media Service (SEMS), for small-scale, rapid production of non-GMP media tested for sterility. With SEMS, customers can request up to 100L of media, to be rapidly manufactured in a Grade A/ISO 5 sterile environment, and have it shipped within 15 business days pending sterility confirmation.
Contamination in culture media can affect cell characteristics such as growth, metabolism, and morphology, contributing to unreliable or erroneous results. This can cause delays in the development and scale-up process. SEMS has been introduced to enable manufacturers to test the feasibility of formulations using sterile cell culture media before scale-up to more costly GMP manufacturing. Sterile media provide an extra measure of control and security for valuable cells and streamline the successful development of cell and gene therapies and biopharmaceutical drugs.
Unlike the sterile-filtered and sterile-tested media currently available in the market, SEMS utilizes isolator technology to provide an aseptic manufacturing environment. SEMS media remain in a Grade A/ISO 5 environment throughout the manufacturing process, reducing the risk of contamination for critical applications. The non-GMP liquid media formulations are manufactured using the same qualified raw materials used for GMP manufacturing and are sterility tested according to USP71 and ISO 13408 requirements.
Erik Vaessen, Ph.D., Executive Director, Life Sciences at FUJIFILM Irvine Scientific commented: “Until now, there has never been a rapid, non-GMP manufacturing service that delivers sterile cell culture media. Sterile Express Media Service is a first-of-its-kind offering that enables FUJIFILM Irvine Scientific customers to use sterile media for trials, which may also help reduce costs associated with developing therapies and biopharmaceutical drugs by reducing contamination risk during the testing phase. We are pleased to offer this innovation to our customers.”
SEMS is part of the FUJIFILM Irvine Scientific group of media services that also include Express Media Service (EMS) for small-scale, rapid production of non-GMP media and Media Development and Optimization Services (MDO) for the development of custom media.