biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Products10.30895/2221-996X-2024-24-2-157-171biopreparat-575Research ArticleТЕМА НОМЕРА: ВЫСОКОТЕХНОЛОГИЧНЫЕ ЛЕКАРСТВЕННЫЕ ПРЕПАРАТЫISSUE TOPIC: ADVANCED THERAPY MEDICINAL PRODUCTSПрименение терапевтических нуклеиновых кислот и интерференции РНК для создания средств персонализированной медициныApplication of therapeutic nucleic acids and RNA interference to create products for personalised medicinehttps://orcid.org/0000-0001-5343-4230ШиловскийИ. П.ShilovskiyI. P.

Шиловский Игорь Петрович, д-р биол. наук

Каширское шоссе, д. 24, Москва, 115522

Igor P. Shilovskiy, Dr. Sci. (Biol.)

24 Kashirskoe Hwy, Moscow 115522

igorshilovski@gmail.comhttps://orcid.org/0009-0007-8916-3322ПасиховГ. Б.PasikhovG. B.

Пасихов Георгий Борисович

Каширское шоссе, д. 24, Москва, 115522

George B. Pasikhov

24 Kashirskoe Hwy, Moscow 115522

george.pasikhov@yandex.ruhttps://orcid.org/0000-0002-8232-6682СмирновВ. В.SmirnovV. V.

Смирнов Валерий Валерьевич, д-р фарм. наук

Каширское шоссе, д. 24, Москва, 115522

ул. Трубецкая, д. 8 стр. 2, Москва, 119991

Valery V. Smirnov, Dr. Sci. (Pharm.)

24 Kashirskoe Hwy, Moscow 115522

8/2 Trubetskaya St., Moscow 119991

vall@mail.mipt.ruhttps://orcid.org/0000-0001-9280-8282КофиадиИ. А.KofiadiI. A.

Кофиади Илья Андреевич, д-р биол. наук

Каширское шоссе, д. 24, Москва, 115522

Ilya A. Kofiadi, Dr. Sci. (Biol.)

24 Kashirskoe Hwy, Moscow 115522

kofiadi@mail.ruhttps://orcid.org/0000-0002-3671-780XПоповаМ. В.PopovaM. V.

Попова Майя Владиславовна

Каширское шоссе, д. 24, Москва, 115522

ул. Островитянова, д. 1, Москва, 117513

Maiia V. Popova

24 Kashirskoe Hwy, Moscow 115522

1 Ostrovityanov St., Moscow 117513

mayhemly@mail.ruhttps://orcid.org/0009-0003-7718-0767СтруеваП. А.StruevaP. A.

Струева Полина Александровна

Каширское шоссе, д. 24, Москва, 115522

ул. Миклухо-Маклая, д. 6, Москва, 117198

Polina A. Strueva

24 Kashirskoe Hwy, Moscow 115522

6 Miklukho-Maklay St., Moscow 117198

polly.strueva@yandex.ruhttps://orcid.org/0000-0003-4961-9640ХаитовМ. Р.KhaitovM. R.

Хаитов Муса Рахимович, д-р мед. наук, проф., член-корр. РАН

Каширское шоссе, д. 24, Москва, 115522

ул. Островитянова, д. 1, Москва, 117513

Musa R. Khaitov, Dr. Sci. (Med.), Professor, Corr. Member of RAS

24 Kashirskoe Hwy, Moscow 115522

1 Ostrovityanov St., Moscow 117513

mr.khaitov@nrcii.ruФедеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентстваРоссияNational Research Center—Institute of ImmunologyRussian FederationФедеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства; Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияNational Research Center—Institute of Immunology; I.M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationФедеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства; Федеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияNational Research Center—Institute of Immunology; N.I. Pirogov Russian National Research Medical UniversityRussian FederationФедеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства; Федеральное государственное автономное образовательное учреждение высшего образования «Российский университет дружбы народов имени Патриса Лумумбы»РоссияNational Research Center—Institute of Immunology; Peoples’ Friendship University of Russia named after Patrice LumumbaRussian Federation202414062024242Высокотехнологичные лекарственные препараты157171Copyright © Шиловский И.П., Пасихов Г.Б., Смирнов В.В., Кофиади И.А., Попова М.В., Струева П.А., Хаитов М.Р., 20242024Шиловский И.П., Пасихов Г.Б., Смирнов В.В., Кофиади И.А., Попова М.В., Струева П.А., Хаитов М.Р.Shilovskiy I.P., Pasikhov G.B., Smirnov V.V., Kofiadi I.A., Popova M.V., Strueva P.A., Khaitov M.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.biopreparations.ru/jour/article/view/575

ВВЕДЕНИЕ. Малые интерферирующие РНК (миРНК) относятся к типу терапевтических нуклеиновых кислот, направленных на подавление экспрессии патогенетически значимых генов посредством механизма интерференции РНК. Однако потенциал препаратов на основе миРНК и их клиническое применение остаются ограниченными, что связано с проблемами биодоступности и иммуногенности миРНК, а также несовершенством систем доставки.ЦЕЛЬ. Обобщить основные достижения в области создания лекарственных препаратов на основе миРНК, в том числе систем их доставки, рассмотреть итоги клинических исследований и обозначить перспективы разработки препаратов данной группы.ОБСУЖДЕНИЕ. Рассмотрены молекулярные основы РНК-интерференции, особенности разработки миРНК и методы их эффективной доставки. Представлены сведения о системах доставки нуклеиновых кислот до клеток-мишеней. Наиболее перспективны невирусные системы доставки: липосомы, экзосомы, наночастицы, полимеры, клеточно-проникающие пептиды и системы с лигандом GalNAc. К основным преимуществам перечисленных систем доставки относятся простота получения комплексов с нуклеиновыми кислотами, возможность модификации и функционализации систем доставки, благоприятный профиль безопасности, способность прохождения биологических барьеров, тропизм к тканям-мишеням. Обобщены результаты клинических исследований за последние несколько лет миРНК-препаратов для лечения метаболических нарушений, инфекционных, онкологических и наследственных заболеваний, патологий органов зрения, почек, печени. Особое внимание уделено препаратам на основе миРНК, которые проходят клинические исследования (более 10 препаратов), а также одобренным для клинического применения (6 препаратов), в том числе первому зарегистрированному российскому препарату на основе миРНК — МИР 19.ЗАКЛЮЧЕНИЕ. Препараты миРНК  — перспективные средства персонализированной медицины, демонстрирующие возможности для терапии широкого спектра различных патологий. Дальнейшие исследования препаратов данной группы должны быть направлены на совершенствование технологии получения молекул миРНК — для увеличения биодоступности и периода полувыведения — и систем их доставки в целевые клетки — для снижения риска токсичности и повышения эффективности.

INTRODUCTION. Small interfering RNAs (siRNAs) are among the most promising types of therapeutic nucleic acids aiming at the inhibition of pathogenetically relevant gene expression through the RNA interference mechanism. However, the limited bioavailability and immunogenicity of siRNAs and imperfect delivery systems hinder the clinical potential and applicability of siRNA medicinal products.AIM. This study aimed to summarise recent advances in the development of siRNA medicinal products and the corresponding delivery systems, review clinical trial results, and outline future development prospects for these medicinal products.DISCUSSION. This article covers the molecular mechanisms underlying RNA interference, the considerations for siRNA development, and the techniques for effective siRNA delivery. The article dwells upon various systems for nucleic acid delivery to targeted cells. The most promising delivery systems are non-viral systems, including liposomes, exosomes, nanoparticles, polymers, cell-penetrating peptides, and GalNAc ligands. Their main advantages include their ease of complexation with nucleic acids, modification and functionalization potential, favourable safety profile, ability to cross biological barriers, and tropism to target tissues. The article summarises the information that has accumulated over the past few years in clinical trials of siRNA medicinal products for a range of conditions, including metabolic disorders, infections, and cancers, as well as hereditary, ophthalmic, renal, and hepatic diseases. Special attention is paid to siRNA medicinal products undergoing clinical trials (over 10 products) and approved for clinical use (6 products, including MIR 19, the first authorised Russian siRNA medicinal product).CONCLUSION. Ultimately, siRNA medicinal products are a promising tool for personalised medicine, exhibiting therapeutic potential for a wide range of pathological conditions. Further studies of siRNA medicinal products should aim at improving siRNA production technology to increase their bioavailability and half-life period. In addition, these studies should aim at enhancing delivery systems for these products to mitigate toxicity risks and maximise efficacy.

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