Specific gene blockade shows that peptide nucleic acids readily enter neuronal cells in vivo

Beth M. Tyler, Daniel J. McCormick, Clark V. Hoshall, Christopher L. Douglas, Karen Jansen, Benjamin W. Lacy, Bernadette Cusack, Elliott Richelson

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Peptide nucleic acids (PNAs) are DNA analogs that can hybridize to complementary sequences with high affinity and stability. Here, we report the first evidence of intracellular delivery of PNAs in vivo. Two CNS receptors, an opioid (mu) and a neurotensin (NTR-1), were targeted independently by repeated microinjection of PNAs into the periaqueductal gray. Behavioral responses to neurotensin (antinociception and hypothermia) and morphine (antinociception) were lost in a specific manner. Binding studies confirmed a large reduction in receptor sites. The loss of behavioral responses was long lasting but did fully recover. The implications of specifically and readily turning off gene expression in vivo are profound.

Original languageEnglish (US)
Pages (from-to)280-284
Number of pages5
JournalFEBS Letters
Volume421
Issue number3
DOIs
StatePublished - Jan 16 1998

Keywords

  • Antinociception
  • Hypothermia
  • Morphine
  • Neurotensin
  • Peptide nucleic acid

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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