title: 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.
authors.affiliation: Novosibirsk State University, Novosibirsk, 630090, Russia. markel@bionet.nsc.ru.
authors.forename: M N
authors.initials: MN
authors.lastname: Repkova
authors.forename: A S
authors.initials: AS
authors.lastname: Levina
authors.forename: A A
authors.initials: AA
authors.lastname: Seryapina
authors.forename: N V
authors.initials: NV
authors.lastname: Shikina
authors.forename: E V
authors.initials: EV
authors.lastname: Bessudnova
authors.forename: V F
authors.initials: VF
authors.lastname: Zarytova
authors.forename: A L
authors.initials: AL
authors.lastname: Markel
mesh_terms: D000818:Animals; D015316:Genetic Therapy; D006973:Hypertension / Q000628:therapy*; D008297:Male; D009841:Oligonucleotides / Q000008:administration & dosage*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014025:Titanium / Q000008:administration & dosage
chemical_list: D009841:Oligonucleotides; C009495:titanium dioxide; D014025:Titanium; D007703:Peptidyl-Dipeptidase A