Peptide nucleic acids specifically cause antigene effects in vivo by systemic injection

Beth M. McMahon, Jennifer A. Stewart, M. D. Bitner, Abdul Fauq, Daniel J. McCormick, Elliott Richelson

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Peptide nucleic acids (PNAs) are uncharged DNA analogs that hybridize to complementary sequences with high affinity and stability. We previously showed that PNAs, after intraperitoneal injection into rats, are effective antisense compounds in vivo. The present study was designed to test whether PNAs also have antigene effects in vivo. The renin-angiotensin system is critical in the control of blood pressure. We designed and synthesized sense (antigene) PNAs to angiotensinogen, which is the precursor protein that leads to angiotensin I and II. Spontaneously hypertensive rats received intraperitoneal injections of either 20 mg/kg sense-angiotensinogen-PNA, mismatch-angiotensinogen PNA, or saline. Only the sense-angiotensinogen PNA treatment resulted in a significant decrease in plasma angiotensin I, systolic blood pressure, and liver and brain angiotensinogen mRNA levels. Thus, these results demonstrate on the molecular, protein, and physiological levels that antigene PNAs are effective in vivo upon systemic administration.

Original languageEnglish (US)
Pages (from-to)325-337
Number of pages13
JournalLife Sciences
Volume71
Issue number3
DOIs
StatePublished - Jun 7 2002

Keywords

  • Angiotensin
  • Gene therapy
  • Hypertension
  • Peptide nucleic acids

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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