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

作　　者：QINGYANG ZHANG SHUXIAN HUANG DAN WENG 

机构地区：[1]School of Environmental and Biological Engineering,Nanjing University of Science&Technology,Nanjing,210000,China

出　　处：《BIOCELL》2024年第10期1443-1453,共11页生物细胞(英文)

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

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.

关 键 词：Huntington’s disease Neurodegenerative disease RNA therapy TRANS-SPLICING Spliceosome-mediated RNA trans-splicing 

分 类 号：R73[医药卫生—肿瘤]