Transcription activator-like effector nucleases (TALENs) are a new class of 
engineered nucleases that are easier to design to cleave at desired sites in a 
genome than previous types of nucleases. We report here the use of TALENs to 
rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic 
cells or human pluripotent stem cells, the latter for which we differentiated 
both the targeted lines and isogenic control lines into various metabolic cell 
types. We demonstrate cell-autonomous phenotypes directly linked to 
disease-dyslipidemia, insulin resistance, hypoglycemia, lipodystrophy, 
motor-neuron death, and hepatitis C infection. We found little evidence of TALEN 
off-target effects, but each clonal line nevertheless harbors a significant 
number of unique mutations. Given the speed and ease with which we were able to 
derive and characterize these cell lines, we anticipate TALEN-mediated genome 
editing of human cells becoming a mainstay for the investigation of human 
biology and disease.