Antisense and antigene inhibition of gene expression by cell-permeable oligonucleotide-oligospermine conjugates

Keith T. Gagnon, Jonathan K. Watts, Hannah M. Pendergraff, Christophe Montaillier, Danielle Thai, Pierre Potier, David R. Corey

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Oligonucleotides and their derivatives are a proven chemical strategy for modulating gene expression. However, their negative charge remains a challenge for delivery and target recognition inside cells. Here we show that oligonucleotide-oligospermine conjugates (Zip nucleic acids or ZNAs) can help overcome these shortcomings by serving as effective antisense and antigene agents. Conjugates containing DNA and locked nucleic acid (LNA) oligonucleotides are active, and oligospermine conjugation facilitates carrier-free cell uptake at nanomolar concentrations. Conjugates targeting the CAG triplet repeat within huntingtin (HTT) mRNA selectively inhibit expression of the mutant huntingtin protein. Conjugates targeting the promoter of the progesterone receptor (PR) function as antigene agents to block PR expression. These observations support further investigation of ZNA conjugates as gene silencing agents.

Original languageEnglish (US)
Pages (from-to)8404-8407
Number of pages4
JournalJournal of the American Chemical Society
Volume133
Issue number22
DOIs
StatePublished - Jun 8 2011

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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