CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts of familial ALS patients bearing SOD1(+/A272C) and FUS+/G1566A mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq) analysis of motor neurons derived from SOD1(+/A272C) and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.National Basic Research Program of China (973 Program) [2015CB964800, 2014CB964600, 2014CB910503]; National High Technology Research and Development Program of China [2015AA020307]; CAS [XDA01020312, KJZDEW-TZ-L05, CXJJ-16M271]; National Natural Science Foundation of China [1625009, 81330008, 31222039, 81371342, 81300261, 81300677, 81271266, 81471414, 81422017, 81401159, 31671429, 81601233, 81671377, 31601109, 31601158]; Beijing Natural Science Foundation [7141005, 5142016]; Program of Beijing Municipal Science and Technology Commission [Z151100003915072]; Key Research Program of the Chinese Academy of Sciences [KJZDEW-TZ-L05]; Thousand Young Talents Program of China; State Key Laboratory of Stem Cell and Reproductive Biology [2016SRLabKF13]; UCAM; G. Harold and LeilaY. Mathers Charitable Foundation; Leona M. and Harry B. Helmsley Charitable Trust [2012-PG-MED002]; Moxie FoundationSCI(E)中国科学引文数据库(CSCD)ARTICLE5365-378