Peptide nucleic acids specifically cause antigene effects in vivo by systemic injection.
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.
McMahon
Beth M
BM
Laboratory of Neuropsychopharmacology, Mayo Foundation for Medical and Educational Research, Jacksonville, FL 32224, USA. mcmahon.beth@mayo.edu
Stewart
Jennifer A
JA
Bitner
M D
MD
Fauq
Abdul
A
McCormick
Daniel J
DJ
Richelson
Elliott
E
D000704:Analysis of Variance; D000803:Angiotensin I / Q000097:blood*; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018390:Gene Targeting; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020135:Peptide Nucleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR
D020135:Peptide Nucleic Acids; D012333:RNA, Messenger; D000808:Angiotensinogen; D000803:Angiotensin I