Gene Targeting Techniques for Huntington's Disease


Huntington’s disease (HD) is an autosomal neurodegenerative disorder caused by extended trinucleotide CAG repetition in the HTT gene. Although this mutation in the HTT gene is mostly associated with neurological and physical symptoms that HD typically exhibits, wild-type Huntingtin protein (HTT) is involved in a variety of cellular functions such as vesicle transportation, cell division, transcription regulation, autophagy, and tissue maintenance. The main cause of HD symptoms is due to aggregation and accumulation of mutant HTT (mHTT) proteins in neurons. 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 SNPs and haplogroup analysis, and the possible limitations of targeting mHTT is also discussed. Additionally, this review discusses am potential appliction of recent CRISPR prime editing technology in treating HD.