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

ABSTRACT: 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.

SUBMITTER: Wang L

PROVIDER: S-EPMC5413600 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Wang Lixia L Yi Fei F Fu Lina L Yang Jiping J Wang Si S Wang Zhaoxia Z Suzuki Keiichiro K Sun Liang L Xu Xiuling X Yu Yang Y Qiao Jie J Belmonte Juan Carlos Izpisua JCI Yang Ze Z Yuan Yun Y Qu Jing J Liu Guang-Hui GH

Protein & cell 20170411 5

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 <sup>+/A272C</sup> and FUS <sup>+/G1566A</sup> mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. ...[more]

PMID: 28401346

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High-Efficiency CRISPR/Cas9-Mediated Correction of a Homozygous Mutation in Achromatopsia-Patient-Derived iPSCs.

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Human Motor Neurons With SOD1-G93A Mutation Generated From CRISPR/Cas9 Gene-Edited iPSCs Develop Pathological Features of Amyotrophic Lateral Sclerosis.

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CRISPR-mediated gene correction links the ATP7A M1311V mutations with amyotrophic lateral sclerosis pathogenesis in one individual.

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Amyotrophic lateral sclerosis

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Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls. Keywords: other

2003-11-14 | GSE833 | GEO

Amyotrophic lateral sclerosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2012-07-26 | GSE39644 | GEO

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