通过基因敲除和替换手术治疗视网膜色素变性的常染色体显性视网膜炎。

IF 3.9 3区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Human gene therapy Pub Date : 2024-03-01 DOI:10.1089/hum.2023.201

Xuehan Sun, Chen Liang, Yangcan Chen, Tongtong Cui, Jiabao Han, Moyu Dai, Ying Zhang, Qi Zhou, Wei Li

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引用次数: 0

摘要

Rhodopsin（RHO）基因突变是常染色体显性色素性视网膜炎（adRP）的主要病因。鉴于功能增益突变的多样性，针对特定序列的治疗策略面临着巨大挑战。在此，我们提供了一种通用方法来解决这一问题：我们设计了一种基于CRISPR-Cas12i的、不依赖突变的基因敲除和替换复合疗法，由双AAV8系统携带。在这项研究中，我们成功地延缓了经典小鼠疾病模型 RhoP23H 和 RhoP347S（我们开发的一种新的原生小鼠突变模型）视网膜变性的进展。我们的研究拓展了未来治疗视网膜色素变性（RHO介导的常染色体显性遗传性视网膜炎）的潜在选择范围。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Knockout and Replacement Gene Surgery to Treat Rhodopsin-Mediated Autosomal Dominant Retinitis Pigmentosa.

Mutations in the rhodopsin (RHO) gene are the predominant causes of autosomal dominant retinitis pigmentosa (adRP). Given the diverse gain-of-function mutations, therapeutic strategies targeting specific sequences face significant challenges. Here, we provide a universal approach to conquer this problem: we have devised a CRISPR-Cas12i-based, mutation-independent gene knockout and replacement compound therapy carried by a dual AAV2/8 system. In this study, we successfully delayed the progression of retinal degeneration in the classic mouse disease model Rho^P23H, and also Rho^P347S, a new native mouse mutation model we developed. Our research expands the horizon of potential options for future treatments of RHO-mediated adRP.

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来源期刊

Human gene therapy 医学-生物工程与应用微生物

CiteScore

6.50

自引率

4.80%

发文量

131

审稿时长

4-8 weeks

期刊介绍： Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases.