Molecular Biology Department, Laval University, Quebec, QC G1V 0A6, Canada.
CHU de Québec Research Center, Laval University, Quebec, QC G1V 4G2, Canada.
Cells. 2023 Dec 22;13(1):31. doi: 10.3390/cells13010031.
We report the first correction from prime editing a mutation in the gene, paving the way to gene therapies for RYR1-related myopathies. The 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 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.
我们报告了首次使用 Prime 编辑纠正 基因突变，为 RYR1 相关肌病的基因治疗铺平了道路。该基因编码一种名为 Ryanodine 受体 1 的钙通道，该通道在骨骼肌纤维中表达。该通道的失活导致患者肌肉无力，从而导致运动障碍。目前，这些疾病主要由点突变引起，尚无有效的治疗方法。Prime 编辑允许对 DNA 中的精确核苷酸进行修饰。我们的结果显示，通过 RNA 递送 Prime 编辑组件，可将人类成肌细胞中的 基因 T4709M 突变校正 59%。需要注意的是，T4709M 是隐性的，因此，杂合突变的人是健康的。这些结果首次证明，纠正 RYR1 基因中的突变是可能的。
