biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Products10.30895/2221-996X-2024-24-2-140-156biopreparat-578Research ArticleТЕМА НОМЕРА: ВЫСОКОТЕХНОЛОГИЧНЫЕ ЛЕКАРСТВЕННЫЕ ПРЕПАРАТЫISSUE TOPIC: ADVANCED THERAPY MEDICINAL PRODUCTSМикроРНК-направленные олигонуклеотидные конструкции с различным механизмом действия для эффективного подавления процессов канцерогенезаmiRNA-targeting oligonucleotide constructs with various mechanisms of action as effective inhibitors of carcinogenesishttps://orcid.org/0000-0001-7767-7712МирошниченкоС. К.MiroshnichenkoS. K.

Мирошниченко Светлана Константиновна, канд. биол. наук

проспект Академика Лаврентьева, д. 8, г. Новосибирск, 630090

Svetlana K. Miroshnichenko, Cand. Sci. (Biol.)

8 Academician Lavrentyev Ave, Novosibirsk 630090

sveta-mira@yandex.ruhttps://orcid.org/0000-0002-1460-4345ПатутинаО. А.PatutinaO. A.

Патутина Ольга Александровна, канд. биол. наук

проспект Академика Лаврентьева, д. 8, г. Новосибирск, 630090

Olga A. Patutina, Cand. Sci. (Biol.)

8 Academician Lavrentyev Ave, Novosibirsk 630090

patutina@niboch.nsc.ruhttps://orcid.org/0000-0003-4044-1049ЗенковаМ. А.ZenkovaM. A.

Зенкова Марина Аркадьевна, д-р биол. наук, проф., член-корр. РАН

проспект Академика Лаврентьева, д. 8, г. Новосибирск, 630090

Marina A. Zenkova, Dr. Sci. (Biol.), Professor, Corr. Member of RAS

8 Academician Lavrentyev Ave, Novosibirsk 630090

marzen@niboch.nsc.ruФедеральное государственное бюджетное учреждение науки Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наукРоссияInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of SciencesRussian Federation202404062024242Высокотехнологичные лекарственные препараты140156Copyright © Мирошниченко С.К., Патутина О.А., Зенкова М.А., 20242024Мирошниченко С.К., Патутина О.А., Зенкова М.А.Miroshnichenko S.K., Patutina O.A., Zenkova M.A.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/578

ВВЕДЕНИЕ. Развитие злокачественных новообразований ассоциировано с изменениями в экспрессии малых некодирующих РНК (микроРНК), что подчеркивает необходимость исследований в области разработки микроРНК-направленных ингибиторов как перспективного подхода к лечению онкологических заболеваний.ЦЕЛЬ. Сравнительная оценка и определение возможностей практического применения существующих в настоящее время стратегий подавления функциональной активности опухоль-ассоциированных микроРНК, основанных на использовании терапевтических нуклеиновых кислот.ОБСУЖДЕНИЕ. Проведен анализ известных ингибиторов микроРНК на основе олигонуклеотидов, характеризующихся различными механизмами действия. Ингибиторы микроРНК по механизму действия можно условно разделить на две группы. Первая группа соединений оказывает опосредованное ингибирующее влияние либо за счет блокирования функциональных связей между микроРНК и определенными мРНК-мишенями путем использования микроРНК-маскирующих олигонуклеотидов, либо за счет введения мутаций в гены микроРНК и нарушения процессов их биосинтеза с помощью системы CRISPR/Cas. Эти стратегии обладают сравнительно высоким биологическим потенциалом, однако в большинстве случаев используются в качестве поисковых инструментов для изучения функциональной роли микроРНК и определения их молекулярных взаимодействий в процессах канцерогенеза. Вторая группа олигонуклеотидных конструкций взаимодействует с микроРНК-мишенями напрямую, приводя к их стерическому блокированию или деградации. Такие микроРНК-связывающие олигонуклеотидные конструкции представлены множеством структурных вариантов, включая микроРНК-спонжи, РНК-зипперы, антисмысловые олигонуклеотиды и миРНКазы, демонстрирующие высокий терапевтический потенциал in vitro и in vivo.ЗАКЛЮЧЕНИЕ. Представленный анализ биологических свойств, терапевтического потенциала и ключевых преимуществ разработанных микроРНК-направленных олигонуклеотидных конструкций позволяет обозначить области их потенциального практического применения при лечении злокачественных новообразований.

INTRODUCTION. The development of malignant neoplasms is associated with changes in the expression of small non-coding RNAs (miRNAs). This emphasises the need for research into the development of miRNA-targeted inhibitors as a promising approach to cancer treatment.AIM. This study aimed to compare current strategies for suppressing the functional activity of tumour-associated miRNAs based on the use of therapeutic nucleic acids and to determine the application potential of these strategies.DISCUSSION. This study analysed known oligonucleotide-based miRNA inhibitors with different mechanisms of action. Based on their mechanism of action, miRNA-targeted inhibitors can be classified into two groups. The first group of miRNA-targeted inhibitors exhibits an indirect inhibitory effect, either by blocking functional connections between miRNAs and specific mRNA targets through the use of miRNA-masking oligonucleotides or by introducing mutations into miRNA genes and disrupting gene biosynthesis processes through the use of the CRISPR/Cas system. Despite their relatively high biological potential, these strategies are mostly used as search tools to study miRNA functional roles and molecular interactions in carcinogenesis. The second group of oligonucleotide constructs interacts with miRNA targets directly, which leads to steric blocking or degradation of oncogenic microRNAs. These miRNA-binding oligonucleotide constructs come in a variety of structural variants, including miRNA sponges, RNA zippers, antisense oligonucleotides, and miRNases, which demonstrate high therapeutic potential in vitro and in vivo.CONCLUSION. The described analysis of the biological properties, therapeutic potential, and key advantages of the developed miRNA-targeted oligonucleotide constructs helps outline the areas for their potential practical application in cancer treatment.

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