Spliceosome-mediated RNA trans-splicing: a strategy for Huntington’s disease gene therapy

作     者：QINGYANG ZHANG SHUXIAN HUANG DAN WENG 

作者机构：School of Environmental and Biological EngineeringNanjing University of Science&TechnologyNanjing210000China 

出 版 物：《BIOCELL》 (生物细胞(英文))

年 卷 期：2024年第48卷第10期

页      面：1443-1453页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：National Natural Science Foundation of China under Grant 22376100 

主　　题：Huntington’s disease Neurodegenerative disease RNA therapy Trans-splicing Spliceosome-mediated RNA trans-splicing 

摘      要：Huntington’s disease (HD) is a debilitating neurodegenerative disorder caused by an abnormal expansion of CAG repeats (Cytosine, Adenine, Guanine) in the huntingtin gene (HTT). This mutation leads to the production of a mutant huntingtin protein, resulting in neuronal dysfunction and cell death. Current treatments primarily focus on symptomatic relief and do not address the underlying genetic cause. This review explores spliceosome-mediated RNA trans-splicing (SMaRT) therapy as an innovative and potential approach for HD treatment. SMaRT leverages the cell’s natural splicing machinery to correct mutant mRNA, thereby reducing toxic protein levels while restoring functional protein production. We compare SMaRT with other gene therapy strategies, such as antisense oligonucleotides, RNA interference, and CRISPR-based systems, highlighting SMaRT’s dual-action mechanism and its potential advantages in clinical applications. Additionally, we discuss the challenges and future directions for SMaRT therapy, emphasizing the need for further research to optimize its efficacy and safety. This review aims to provide a comprehensive overview of current and emerging therapies for HD, with a focus on the innovative potential of SMaRT.