Massengill Michael T, Young Brianna M, Lewin Alfred S, Ildefonso Cristhian J
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA.
Department of Ophthalmology, University of Florida College of Medicine, Gainesville, FL, USA.
Methods Mol Biol. 2019;1937:235-258. doi: 10.1007/978-1-4939-9065-8_15.
Recombinant adeno-associated virus (rAAV) has become an important gene delivery vector for the treatment of inherited retinal degenerative diseases. Many of the mutations leading to retinal degeneration are inherited in an autosomal-dominant pattern and can produce toxic gain-of-function and/or dominant-negative effects. Here we describe an allele-independent gene therapy strategy with rAAV to treat autosomal-dominant retinal degenerative diseases. In this methodology, we co-deliver a short-hairpin RNA (shRNA) to inhibit expression of both the toxic and (WT) copies of the gene as well as an shRNA-resistant cDNA for functional gene replacement with a rAAV.
重组腺相关病毒（rAAV）已成为治疗遗传性视网膜退行性疾病的重要基因递送载体。许多导致视网膜变性的突变以常染色体显性模式遗传，并且可产生毒性功能获得和/或显性负性效应。在此，我们描述了一种使用rAAV治疗常染色体显性视网膜退行性疾病的等位基因非依赖性基因治疗策略。在这种方法中，我们共同递送一种短发夹RNA（shRNA）以抑制该基因的毒性拷贝和（野生型）拷贝的表达，以及一种抗shRNA的cDNA，用于用rAAV进行功能性基因替代。
