Gemstone Honors Program, University of Maryland, College Park, MD 20742, United States.
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, United States.
Ageing Res Rev. 2021 Sep;70:101385. doi: 10.1016/j.arr.2021.101385. Epub 2021 Jun 5.
Huntington's disease (HD) is an autosomal neurodegenerative disorder caused by extended trinucleotide CAG repetition in the HTT gene. Wild-type huntingtin protein (HTT) is essential, involved in a variety of crucial cellular functions such as vesicle transportation, cell division, transcription regulation, autophagy, and tissue maintenance. The mutant HTT (mHTT) proteins in the body interfere with HTT's normal cellular functions and cause additional detrimental effects. In this review, we discuss multiple approaches targeting DNA and RNA to reduce mHTT expression. These approaches are categorized into non-allele-specific silencing and allele-specific-silencing using Single Nucleotide Polymorphisms (SNPs) and haplogroup analysis. Additionally, this review discusses a potential application of recent CRISPR prime editing technology in targeting HD.
亨廷顿病（HD）是一种常染色体神经退行性疾病，由 HTT 基因中三核苷酸 CAG 重复扩展引起。野生型亨廷顿蛋白（HTT）是必不可少的，参与多种关键的细胞功能，如囊泡运输、细胞分裂、转录调控、自噬和组织维持。体内的突变 HTT（mHTT）蛋白干扰 HTT 的正常细胞功能，并造成额外的有害影响。在这篇综述中，我们讨论了多种针对 DNA 和 RNA 的方法来降低 mHTT 的表达。这些方法分为非等位基因特异性沉默和等位基因特异性沉默，使用单核苷酸多态性（SNPs）和单倍型分析。此外，本综述还讨论了最近的 CRISPR 先导编辑技术在靶向 HD 中的潜在应用。
