PTC124-Mediated Translational Readthrough of a Nonsense Mutation Causing Usher Syndrome Type 1C

被引：72
作者：
Goldmann, T. [1 ]
Overlack, N. [1 ]
Wolfrum, U. [1 ]
Nagel-Wolfrum, K. [1 ]
机构：
[1] Johannes Gutenberg Univ Mainz, Inst Zool, Dept Cell & Matrix Biol, D-55099 Mainz, Germany
来源：
HUMAN GENE THERAPY | 2011年 / 22卷 / 05期
关键词：
HUMAN GENETIC-DISEASES; CYSTIC-FIBROSIS; PHOTORECEPTOR CELLS; RECESSIVE DEAFNESS; PROTEIN COMPLEXES; ATALUREN PTC124; READ-THROUGH; IN-VITRO; RETINA; HARMONIN;
D O I：
10.1089/hum.2010.067
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
We investigated the therapeutic potential of the premature termination codon (PTC) readthrough-inducing drug PTC124 in treating the retinal phenotype of Usher syndrome, caused by a nonsense mutation in the USH1C gene. Applications in cell culture, organotypic retina cultures, and mice in vivo revealed significant readthrough and the recovery of protein function. In comparison with other readthrough drugs, namely the clinically approved readthrough-inducing aminoglycoside gentamicin, PTC124 exhibits significant better retinal biocompatibility. Its high readthrough efficiency in combination with excellent biocompatibility makes PTC124 a promising therapeutic agent for PTCs in USH1C, as well as other ocular and nonocular genetic diseases.
引用
收藏
页码：537 / 547
页数：11
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