期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 3, 期 -, 页码 -出版社
CELL PRESS
DOI: 10.1038/mtna.2014.23
关键词
antisense oligonucleotide; cardiac; short ASO; skeletal muscle; SMA mouse model; SMN2; spinal muscular atrophy; splicing
资金
- National Institutes of Health (NIH) [NS072259, NS055925]
- Salsbury Endowment
- NIH [R01NS060926]
- Families of SMA [DID1214]
- Muscular Dystrophy Association [255785]
Recent reports underscore the unparalleled potential of antisense-oligonucleotide (ASO)-based approaches to ameliorate various pathological conditions. However, in vivo studies validating the effectiveness of a short ASO (<10-mer) in the context of a human disease have not been performed. One disease with proven amenability to ASO-based therapy is spinal muscular atrophy (SMA). SMA is a neuromuscular disease caused by loss-of-function mutations in the survival motor neuron 1 (SMN1) gene. Correction of aberrant splicing of the remaining paralog, SMN2, can rescue mouse models of SMA. Here, we report the therapeutic efficacy of an 8-mer ASO (3UP8i) in two severe models of SMA. While 3UP8i modestly improved survival and function in the more severe Taiwanese SMA model, it dramatically increased survival, improved neuromuscular junction pathology, and tempered cardiac deficits in a new, less severe model of SMA. Our results expand the repertoire of ASO-based compounds for SMA therapy, and for the first time, demonstrate the in vivo efficacy of a short ASO in the context of a human disease.
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