化学
强直性营养不良
DNA
核糖核酸
三核苷酸重复扩增
流式细胞术
分子生物学
计算生物学
细胞生物学
遗传学
生物化学
等位基因
基因
生物
作者
Quentin M. R. Gibaut,Yoshihiro Akahori,Jessica A. Bush,Amirhossein Taghavi,Toru Tanaka,Haruo Aikawa,Lucas S. Ryan,Brian M. Paegel,Matthew D. Disney
摘要
A solid-phase DNA-encoded library (DEL) was studied for binding the RNA repeat expansion r(CUG)exp, the causative agent of the most common form of adult-onset muscular dystrophy, myotonic dystrophy type 1 (DM1). A variety of uncharged and novel RNA binders were identified to selectively bind r(CUG)exp by using a two-color flow cytometry screen. The cellular activity of one binder was augmented by attaching it with a module that directly cleaves r(CUG)exp. In DM1 patient-derived muscle cells, the compound specifically bound r(CUG)exp and allele-specifically eliminated r(CUG)exp, improving disease-associated defects. The approaches herein can be used to identify and optimize ligands and bind RNA that can be further augmented for functionality including degradation.
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