Cell stem cell · 2012
A TALEN genome-editing system for generating human stem cell-based disease models.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Ding Qiurong, Lee Youn-Kyoung, Schaefer Esperance A K, Peters Derek T, Veres Adrian, Kim Kevin, Kuperwasser Nicolas, Motola Daniel L, Meissner Torsten B, Hendriks William T, Trevisan Marta, Gupta Rajat M, Moisan Annie, Banks Eric, Friesen Max, Schinzel Robert T, Xia Fang, Tang Alexander, Xia Yulei, Figueroa Emmanuel, Wann Amy, Ahfeldt Tim, Daheron Laurence, Zhang Feng, Rubin Lee L, Peng Lee F, Chung Raymond T, Musunuru Kiran, Cowan Chad A
Аннотация
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.