Gene targeting techniques for Huntington's disease

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.

Keywords: Allele-specific targeting; Huntington’s disease; Prime editing; SNPs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Gene Expression Regulation
  • Gene Targeting
  • Humans
  • Huntingtin Protein / genetics
  • Huntingtin Protein / metabolism
  • Huntington Disease* / genetics
  • Huntington Disease* / therapy


  • Huntingtin Protein