Antisense Oligonucleotides Immobilized on Silicon-Organic Nanoparticles as a Tool for Prolonged Correction of Hypertensive States

Bull Exp Biol Med. 2019 May;167(1):116-119. doi: 10.1007/s10517-019-04473-5. Epub 2019 Jun 8.

Abstract

We propose an original method for controlling BP by administration of Si~ODN nanocomposites containing antisense oligonucleotides fixed on silicon-organic nanoparticles. ODN in nanocomposites are targeted to mRNA of the genes encoding angiotensin-converting enzyme (ACE1) and type 1 angiotensin-II receptor (AT1A). The experiments were performed on hypertensive ISIAH rats, a genetic model of hypertension. Single inhalation or intraperitoneal administration of the nanocomposites targeted to ACE1 mRNA or ATA1 mRNA, respectively, led to a pronounced decrease (by ~30 mm Hg) in systolic BP in ISIAH rats over a week. The use of scrambled ODN in the nanocomposites had no effect. A decrease in the expression of ACE1 and AT1A genes under the effect of the corresponding antisense ODN was demonstrated, which attested to directed effect of the test preparations.

Keywords: antisense oligonucleotides; arterial hypertension; nanocomposites; silicon-organic nanoparticles.

MeSH terms

  • Amino Acid Transport System A / genetics
  • Amino Acid Transport System A / metabolism
  • Animals
  • Blood Pressure / drug effects*
  • Blood Pressure / genetics
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Hypertension / metabolism
  • Male
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use*
  • Oligonucleotides, Antisense / chemistry*
  • Oligonucleotides, Antisense / therapeutic use*
  • Peptidyl-Dipeptidase A / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Silicon

Substances

  • Amino Acid Transport System A
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Slc38a1 protein, rat
  • Peptidyl-Dipeptidase A
  • Silicon