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Biochemistry (Moscow)

, Volume 82, Issue 4, pp 454–457 | Cite as

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. MarkelEmail author
Article

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.

Keywords

antisense oligonucleotides hypertension ISIAH rats nanocomposites 

Abbreviations

ACE1

angiotensin I-converting enzyme

BP

arterial blood pressure

ISIAH

inherited stress-induced arterial hypertension

NA

nucleic acid

TiO2·PL-DNA

nanocomposites designed by the immobilization of polylysine-containing oligonucleotides on TiO2-nanoparticles

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Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • M. N. Repkova
    • 1
    • 2
  • A. S. Levina
    • 1
    • 2
  • A. A. Seryapina
    • 1
    • 3
  • N. V. Shikina
    • 1
    • 4
  • E. V. Bessudnova
    • 1
    • 4
  • V. F. Zarytova
    • 1
    • 2
  • A. L. Markel
    • 1
    • 3
    Email author
  1. 1.Novosibirsk State UniversityNovosibirskRussia
  2. 2.Institute of Chemical Biology and Fundamental MedicineSiberian Branch of the Russian Academy of SciencesNovosibirskRussia
  3. 3.Institute of Cytology and GeneticsSiberian Branch of the Russian Academy of SciencesNovosibirskRussia
  4. 4.Institute of CatalysisSiberian Branch of the Russian Academy of SciencesNovosibirskRussia

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