Non-coding RNAs provide additional regulatory layers to gene expression as well 
as the potential to being exploited as therapeutic tools. Non-coding RNA-based 
therapeutic approaches have been attempted in dominant diseases, however their 
use for treatment of genetic diseases caused by insufficient gene dosage is 
currently more challenging. SINEUPs are long antisense non-coding RNAs that 
up-regulate translation in mammalian cells in a gene-specific manner, although, 
so far evidence of SINEUP efficacy has only been demonstrated in in vitro 
systems. We now show that synthetic SINEUPs effectively and specifically 
increase protein levels of a gene of interest in vivo. We demonstrated that 
SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human 
disorder leading to amelioration of the disease phenotype. Our results 
demonstrate that SINEUPs act through mechanisms conserved among vertebrates and 
that SINEUP technology can be successfully applied in vivo as a new research and 
therapeutic tool for gene-specific up-regulation of endogenous functional 
proteins.