Gene targeting techniques for Huntington’s disease
Eric Fields, Erik Vaughan, Deepika R. Tripu, Isabelle Lim, Katherine Shrout, Jessica Conway, Nicole Salib, Yubin Lee, Akash Dhamsania, Michael T. Jacobsen, Ashley Woo, Huijing Xue, Kan Cao
Abstract
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.