vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ18.354vavilov-1448Research ArticleРЕПРОДУКТИВНЫЕ ТЕХНОЛОГИИPHYSIOLOGICAL GENETICSАнтисмысловые олигонуклеотиды для исследований механизмов гипертонической болезни и ее терапииAntisense oligonucleotides for the arterial hypertension mechanisms study and therapyКлимовЛ. О.KlimovL. O.

Новосибирск

Novosibirsk

maple1708@mail.ruСеряпинаА. А.SeryapinaA. A.

Новосибирск

Novosibirsk

ЗарытоваВ. Ф.ZarytovaV. F.

Новосибирск

Novosibirsk

ЛевинаА. С.LevinaA. S.

Новосибирск

Novosibirsk

МаркельА. Л.MarkelA. L.

Новосибирск

Novosibirsk

Новосибирский национальный исследовательский государственный университет; Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияNovosibirsk State UniversityRussian FederationНовосибирский национальный исследовательский государственный университет; Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияNovosibirsk State University; Institute of Cytology and Genetics SB RASRussian FederationНовосибирский национальный исследовательский государственный университет; Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наукРоссияNovosibirsk State University; Institute of Chemical Biology and Fundamental Medicine SB RASRussian Federation201806042018222240247Copyright © Климов Л.О., Серяпина А.А., Зарытова В.Ф., Левина А.С., Маркель А.Л., 20182018Климов Л.О., Серяпина А.А., Зарытова В.Ф., Левина А.С., Маркель А.Л.Klimov L.O., Seryapina A.A., Zarytova V.F., Levina A.S., Markel A.L.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1448

Артериальная гипертония – одно из наиболее распространенных хронических заболеваний у взрослых и пожилых людей во всем мире. Эта патология не только снижает качество жизни больных, но и может сопровождаться высоким риском осложнений. Не­ смотря на то что в настоящее время на рынке имеется большое количество антигипертензивных средств, в основном представ­ ляющих собой различные комбинации ингибиторов ренин-ангио­ тензиновой системы, блокаторов адренорецепторов в сочетании с диуретиками, нет общепринятого «золотого стандарта» препара­ тов, которые не имели бы побочных эффектов. В обзоре рассма­ триваются основные аспекты применения антисмысловых олиго­ нуклеотидов в контексте артериальной гипертонии. Известно, что введение антисмысловых олигонуклеотидов – один из способов выключения работы того или иного гена, причем ключевой осо­ бенностью данной методики, отличающей ее от других, является высокая селективность. Однако при несомненных преимуществах метода существуют сложности его применения, связанные как со свойствами самих олигонуклеотидов (недостаточная устойчивость и неэффективное проникновение в клетки), так и с многообразием механизмов возникновения той или иной патологии, в частности гипертонической болезни. В настоящей работе приведена краткая характеристика основных групп мишеней для антисмыслового ингибирования гипертонической болезни. Отдельно рассматрива­ ются новейшие мишени для терапии олигонуклеотидами – регуля­ торные микроРНК. Кроме того, обсуждаются основные модифика­ ции антисмысловых нуклеотидов, разработанные для увеличения длительности эффектов их действия и упрощения приема препа­ ратов данного типа, в частности комбинирование антисмысловых олигонуклеотидов с экспрессирующими векторами на основе аденовируса. Особенное внимание уделено антисмысловым оли­ гонуклеотидам в составе нанокомпозитов. В обзоре обсуждаются результаты применения композитов антисмысловых нуклеотидов к гену ангиотензин-превращающего фермента и наночастиц диоксида титана (TiO2) на крысах линии НИСАГ с индуцированной стрессом артериальной гипертонией. Показано, что использова­ ние антисмысловых олигонуклеотидов продолжает оставаться перспективной методикой для изучения механизмов возникно­ вения различных форм гипертонической болезни, а также имеет высокий потенциал для терапевтического применения.

Arterial hypertension is one of the most common chronic diseases in adults all over the world. This pathology can not only reduce patients’ life quality, but can also be accompanied by a number of complications. Despite the fact that there is a large group of antihypertensive drugs on the market, mainly representing different combinations of inhibitors of the renin-angiotensin system, adrenoreceptor blockers in combination with diuretics, there is no generally accepted “gold standard” for drugs that would not have side effects. The review discusses the main aspects of antisense oligonucleotides use in the context of arterial hypertension. It is well known that the medical implementation of antisense oligonucleotides aims to block the expression of particular genes involved in the pathology development, and a key advantage of this technique is a high selectivity of the effect. However, with the undoubted advantages of the method, there are difficulties in its application, related both to the properties of the oligonucleotides themselves (insufficient stability and poor penetration into cells), and to the variety of mechanisms of the origin of a particular pathology, arterial hypertension, in our case. The review provides a brief description of the main molecular targets for antisense treatment of hypertensive disease. The newest targets for therapy with oligonucleotides – microRNAs – are discussed. The main modifications of antisense nucleotides, designed to increase the duration of their effects and simplify the delivery of this type of drugs to the targets are discussed, in particular, combining antisense oligonucleotides with adenovirus-based expression vectors. Particular attention is given to antisense oligonucleotides in the complex with nanoparticles. The review discusses the results of the use of titanium dioxide (TiO2) containing antisense nanocomposites for the angiotensin converting enzyme in rats with stress induced arterial hypertension (ISIAH). It was shown that the use of antisense oligonucleotides continues to be a promising technique for studying the mechanisms of various forms of hypertensive disease and has a high potential for therapeutic use.

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The authors declare that there are no conflicts of interest present.