Successful Correction by Prime Editing of a Mutation in the RYR1 Gene Responsible for a Myopathy

被引：10

作者：

Godbout, Kelly ^{[1
,2
]}

Rousseau, Joel ^{[2
]}

Tremblay, Jacques P. ^{[1
,2
]}

机构：

[1] Laval Univ, Mol Biol Dept, Quebec City, PQ G1V 0A6, Canada

[2] Laval Univ, CHU Quebec Res Ctr, Res Ctr, Quebec City, PQ G1V 4G2, Canada

来源：

CELLS | 2024年 / 13卷 / 01期

关键词：

prime editing; CRISPR/Cas9; gene editing; gene therapy; RYR1-related diseases; neuromuscular diseases; RYR1; gene; mutations;

D O I：

10.3390/cells13010031

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We report the first correction from prime editing a mutation in the RYR1 gene, paving the way to gene therapies for RYR1-related myopathies. The RYR1 gene codes for a calcium channel named Ryanodine receptor 1, which is expressed in skeletal muscle fibers. The failure of this channel causes muscle weakness in patients, which leads to motor disabilities. Currently, there are no effective treatments for these diseases, which are mainly caused by point mutations. Prime editing allows for the modification of precise nucleotides in the DNA. Our results showed a 59% correction rate of the T4709M mutation in the RYR1 gene in human myoblasts by RNA delivery of the prime editing components. It is to be noted that T4709M is recessive and, thus, persons having a heterozygous mutation are healthy. These results are the first demonstration that correcting mutations in the RYR1 gene is possible.

引用

页数：16

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