Basic & Clinical Medicine ›› 2023, Vol. 43 ›› Issue (4): 674-679.doi: 10.16352/j.issn.1001-6325.2023.04.0674

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Progress in gene therapy mechanism of amyotrophic lateral sclerosis

LI Xiaoguang1*, YANG Lu1, LIU Xudong2, JIA Xinmiao2, YANG Xinzhuang2, CUI Liying1*   

  1. 1. Department of Neurology;
    2. Centre for Medical Science Research,Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730,China
  • Received:2022-12-28 Revised:2023-02-16 Online:2023-04-05 Published:2023-04-03
  • Contact: *;

Abstract: Gene therapy research on amyotrophic lateral sclerosis (ALS) focuses on SOD1, C9ORF72, FUS and ATAX2, et al. According to the mechanism, the pathogenicity of variant genes is mostly acquired by the toxicity gain of function. Two strategies are adopted for the silencing and editing of disease causing genes, namely, naked injection of antisense oligonucleotides (ASO) to induce the degradation of mRNA mediated by RNase H or the silencing of disease causing gene mediated by adeno-associated virus (AAV) to delivery RNA interference (RNAi) to decrease toxicity protein. CRISPR/Cas9 edits and modifies the causing gene to decrease the expression of toxic protein. In addition, there has been much progress in decreasing the level of toxic protein through specific antibodies and metabolic regulators, as well as neuroprotective therapy.

Key words: amyotrophic lateral sclerosis, gene therapy, antisense oligonucleotides, RNA interference, CRISPR-Cas9

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