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

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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.
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