Allele-selective inhibition of mutant huntingtin by peptide nucleic acid-peptide conjugates, locked nucleic acid, and small interfering RNA

Jiaxin Hu, Masayuki Matsui, David R. Corey

Research output: Chapter in Book/Report/Conference proceedingConference contribution

34 Scopus citations

Abstract

The ability to inhibit expression of a mutant allele while retaining expression of a wild-type protein might provide a useful approach to treating Huntington's Disease (HD) and other inherited pathologies. The mutant form of huntingtin (HTT), the protein responsible for HD, is encoded by an mRNA containing an expanded CAG repeat. We demonstrate that peptide nucleic acid conjugates and locked nucleic acids complementary to the CAG repeat selectively block expression of mutant HTT. The selectivity of inhibition is at least as good as that shown by a small interfering RNA targeted to a deletion polymorphism. Our data suggest that antisense oligomers are promising subjects for further development as an anti-HD therapeutic strategy.

Original languageEnglish (US)
Title of host publicationOligonucleotide Therapeutics Fourth Annual Meeting
PublisherBlackwell Publishing Inc.
Pages24-31
Number of pages8
ISBN (Print)9781573317580
DOIs
StatePublished - Sep 1 2009

Publication series

NameAnnals of the New York Academy of Sciences
Volume1175
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Allele selectivity
  • CAG repeat
  • Huntingtin
  • Huntington's disease
  • LNA
  • Locked nucleic acid
  • PNA
  • Peptide nucleic acid
  • SiRNA
  • Trinucleotide repeat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Hu, J., Matsui, M., & Corey, D. R. (2009). Allele-selective inhibition of mutant huntingtin by peptide nucleic acid-peptide conjugates, locked nucleic acid, and small interfering RNA. In Oligonucleotide Therapeutics Fourth Annual Meeting (pp. 24-31). (Annals of the New York Academy of Sciences; Vol. 1175). Blackwell Publishing Inc.. https://doi.org/10.1111/j.1749-6632.2009.04975.x