medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2021.03.47-56medgen-1883Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHРазработка подхода подавления экспрессии гена DUX4 с помощью siРНК в миобластах больных миодистрофией Ландузи-ДежеринаDevelopment of an approach to knockdown of DUX4 gene by siRNA in myoblasts derived from patients with FSHDКривошееваИ. А.KrivosheevaI. A.irina-krivosheeva-92@yandex.ruВяхиреваЮ. В.VyakhirevaYu. V.noemail@neicon.ruТабаковВ. Ю.TabakovV. Yu.noemail@neicon.ruСкобловМ. Ю.SkoblovM. Yu.noemail@neicon.ruФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian Federation2021250620212034756Copyright © Кривошеева И.А., Вяхирева Ю.В., Табаков В.Ю., Скоблов М.Ю., 20212021Кривошеева И.А., Вяхирева Ю.В., Табаков В.Ю., Скоблов М.Ю.Krivosheeva I.A., Vyakhireva Y.V., Tabakov V.Y., Skoblov M.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/1883

Миодистрофия Ландузи-Дежерина (МЛД) - распространённое наследственное заболевание, вызываемое эктопической экспрессией гена DUX4 в мышечных клетках. Метод подавления экспрессии генов при помощи siРНК зарекомендовал себя как эффективный и безопасный способ генной терапии без вмешательства непосредственно в геном. В данной работе мы продемонстрировали возможность трансфекции миобластов человека целевыми siРНК без ущерба жизнеспособности и дальнейшей дифференцировке этих клеток в миотубы. Также мы показали различия в профиле экспрессии генов-мишеней DUX4 между миобластами, полученными от здоровых людей и от пациентов с МЛД. В дальнейшем эти данные могут помочь при разработке эффективных и специфичных siРНК для терапии МЛД.

Facioscapulohumeral dystrophy (FSHD) is a common hereditary disease caused by ectopic expression of the DUX4 gene in muscle cells. The method of suppressing gene expression using siRNA has been shown to be an effective and safe method of gene therapy without interfering directly with the genome. In this work, we demonstrated the possibility of transfecting human myoblasts with targeted siRNAs without compromising the viability and further differentiation of these cells into myotubes. We also showed differences in the expression profile of DUX4 target genes between healthy and patient-derived myoblasts. In the future, these data can be used to develop effective and specific siRNAs for the treatment of FSHD.

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