期刊
NATURE BIOMEDICAL ENGINEERING
卷 6, 期 2, 页码 195-206出版社
NATURE PORTFOLIO
DOI: 10.1038/s41551-021-00774-1
关键词
-
资金
- National Science and Technology Major Projects for Major New Drugs Innovation and Development [2018ZX09711003-001-003, 2018ZX09J18114]
Aminoacyl-tRNA-synthase-tRNA pairs specific for desired unnatural amino acids can read through a nonsense mutation in the dystrophin gene and partially restore muscle function in mice.
Approximately 11% of monogenic diseases involve nonsense mutations that are caused by premature termination codons. These codons can in principle be read-through via the site-specific incorporation of unnatural amino acids to generate full-length proteins with minimal loss of function. Here we report that aminoacyl-tRNA-synthase-tRNA pairs specific for the desired unnatural amino acids can be used to read through a nonsense mutation in the dystrophin gene. We show partial restoration of dystrophin expression in differentiated primary myoblasts (from a mdx mouse model and a patient with Duchenne muscular dystrophy), and restoration of muscle function in two mouse models: mdx mice, via viral delivery of the engineered tRNA-synthase-tRNA pair intraperitoneally or intramuscularly and of the associated unnatural amino acid intraperitoneally; and mice produced by crossing mdx mice and transgenic mice with a chromosomally integrated pair, via intraperitoneal delivery of the unnatural amino acid. The incorporation of unnatural amino acids to restore endogenous protein expression could be explored for therapeutic use. Aminoacyl-tRNA-synthase-tRNA pairs specific for the desired unnatural amino acids can read through a nonsense mutation in the dystrophin gene, and partially restore muscle function in mice.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据