We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Efficacy and long-term safety of CRISPR/Cas9 genome editing in the SOD1-linked mouse models of ALS.
- Authors
Deng, Han-Xiang; Zhai, Hong; Shi, Yong; Liu, Guoxiang; Lowry, Jessica; Liu, Bin; Ryan, Éanna B.; Yan, Jianhua; Yang, Yi; Zhang, Nigel; Yang, Zhihua; Liu, Erdong; Ma, Yongchao C.; Siddique, Teepu
- Abstract
CRISPR/Cas9-mediated genome editing provides potential for therapeutic development. Efficacy and long-term safety represent major concerns that remain to be adequately addressed in preclinical studies. Here we show that CRISPR/Cas9-mediated genome editing in two distinct SOD1-amyotrophic lateral sclerosis (ALS) transgenic mouse models prevented the development of ALS-like disease and pathology. The disease-linked transgene was effectively edited, with rare off-target editing events. We observed frequent large DNA deletions, ranging from a few hundred to several thousand base pairs. We determined that these large deletions were mediated by proximate identical sequences in Alu elements. No evidence of other diseases was observed beyond 2 years of age in these genome edited mice. Our data provide preclinical evidence of the efficacy and long-term safety of the CRISPR/Cas9 therapeutic approach. Moreover, the molecular mechanism of proximate identical sequences-mediated recombination provides mechanistic information to optimize therapeutic targeting design, and to avoid or minimize unintended and potentially deleterious recombination events. Deng et al. assess the effects of CRISPR/Cas9-mediated genome editing in two transgenic mouse models of amyotrophic lateral sclerosis (ALS) for up to 2 years. They find that the genomic editing prevented the development of ALS-like pathology without any notable side-effects, which provides preclinical evidence of the effectiveness and long-term safety of the CRISPR/Cas9 therapeutic approach.
- Subjects
CRISPRS; GENOME editing; GENETICS of amyotrophic lateral sclerosis; PATHOLOGY; DATA analysis
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-01942-4