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

Protein Cell. 2017 May;8(5):365-378. doi: 10.1007/s13238-017-0397-3. Epub 2017 Apr 11.


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.

Keywords: ALS; CRISPR/Cas9; gene correction; iPSC disease modeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis* / genetics
  • Amyotrophic Lateral Sclerosis* / metabolism
  • Amyotrophic Lateral Sclerosis* / therapy
  • Cell Line
  • Clustered Regularly Interspaced Short Palindromic Repeats*
  • Genetic Therapy*
  • Genome-Wide Association Study
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Mutation, Missense
  • RNA-Binding Protein FUS* / genetics
  • RNA-Binding Protein FUS* / metabolism
  • Superoxide Dismutase-1* / genetics
  • Superoxide Dismutase-1* / metabolism


  • FUS protein, human
  • RNA-Binding Protein FUS
  • SOD1 protein, human
  • Superoxide Dismutase-1