Toward gene therapy of hypertension: Experimental study on hypertensive ISIAH rats

M. N. Repkova, A. S. Levina, A. A. Seryapina, N. V. Shikina, E. V. Bessudnova, V. F. Zarytova, A. L. Markel

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

TiO2-based nanocomposites were prepared to deliver oligonucleotides into cells. The nanocomposites were designed by the immobilization of polylysine-containing oligonucleotides on TiO2-nanoparticles (TiO2·PL-DNA). We showed for the first time the possibility of using the proposed nanocomposites for treatment of hypertensive disease by introducing them into hypertensive ISIAH rats developed as a model of stress-sensitive arterial hypertension. The mRNA of the gene encoding angiotensin I-converting enzyme (ACE1) involved in the synthesis of angiotensin II was chosen as a target. Administration (intraperitoneal injection and inhalation) of the nanocomposite showed a significant (by 20-30 mm Hg) decrease in systolic blood pressure when the nanocomposite contained the ACE1 gene-targeted oligonucleotide. When using the oligonucleotide with a random sequence, no effect was observed. Further development and improvement of the inhalation nanocomposite drug delivery to systemic hypertensive disease treatment promises new possibilities for clinical practice.

Original languageEnglish
Pages (from-to)454-457
Number of pages4
JournalBiochemistry (Moscow)
Volume82
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017

Keywords

  • antisense oligonucleotides
  • hypertension
  • ISIAH rats
  • nanocomposites
  • NANOPARTICLES
  • NANOCOMPOSITES
  • INFLUENZA-A VIRUS
  • ANTISENSE
  • DISEASE
  • STRESS
  • BLOOD-PRESSURE
  • DELIVERY

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