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

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.

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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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Correspondence to A. L. Markel.

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Published in Russian in Biokhimiya, 2017, Vol. 82, No. 4, pp. 620-625.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM16-314, December 5, 2016.

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Repkova, M.N., Levina, A.S., Seryapina, A.A. et al. Toward gene therapy of hypertension: Experimental study on hypertensive ISIAH rats. Biochemistry Moscow 82, 454–457 (2017). https://doi.org/10.1134/S000629791704006X

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Keywords

  • antisense oligonucleotides
  • hypertension
  • ISIAH rats
  • nanocomposites