Gene Targeting by Triple Helix-Forming Oligonucleotides

Alokes Majumdar, Nitin Puri, Nicholas McCollum, Sally Richards, Bernard Cuenoud, Paul Miller, Michael M. Seidman

Research output: Contribution to journalArticle

Abstract

Effective gene targeting reagents would have widespread utility for genomic manipulation including transgenic cell and animal construction and for gene therapy. They would also be useful in basic research as probes of chromatin structure, and as tools for studying the repair and mutagenesis of targeted DNA damage. We are developing triple helix-forming oligonucleotides (TFOs) for gene targeting in living mammalian cells. Challenges to TFO bioactivity include the impediments to the biochemistry of triplex formation presented by the physiological environment and the charge repulsion between the duplex and the third strand. In addition, there are biological constraints to target access imposed by mammalian chromatin structure. Here we describe the oligonucleotide modification format that appears to support biological activity of TFOs. In addition we show that manipulation of the cell biology, specifically the cell cycle, has a dramatic influence on TFO bioactivity.

Original languageEnglish (US)
Pages (from-to)141-153
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume1002
DOIs
StatePublished - Jan 1 2003

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Keywords

  • Cell cycle
  • DNA triple helix
  • Gene targeting
  • Psoralen crosslinking

ASJC Scopus subject areas

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

Cite this

Majumdar, A., Puri, N., McCollum, N., Richards, S., Cuenoud, B., Miller, P., & Seidman, M. M. (2003). Gene Targeting by Triple Helix-Forming Oligonucleotides. Annals of the New York Academy of Sciences, 1002, 141-153. https://doi.org/10.1196/annals.1281.013