Toward Gene Therapy of Hypertension: Experimental Study on Hypertensive ISIAH Rats

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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, and A. L. Markel^1,3*

¹Novosibirsk State University, 630090 Novosibirsk, Russia; E-mail: markel@bionet.nsc.ru

²Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; E-mail: repk@niboch.nsc.ru

³Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; E-mail: icg-adm@bionet.nsc.ru

⁴Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; E-mail: bic@catalysis.ru

^* To whom correspondence should be addressed.

Received September 27, 2016; Revision received November 7, 2016

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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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KEY WORDS: antisense oligonucleotides, hypertension, ISIAH rats, nanocomposites

DOI: 10.1134/S000629791704006X

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