vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biologyvestnik-bio-msu-656Research ArticleОБЗОРREVIEWМЕТОДЫ ГЕННОЙ ТЕРАПИИ ДЛЯ ЛЕЧЕНИЯ ВРОЖДЕННОГО БУЛЛЕЗНОГО ЭПИДЕРМОЛИЗАMETHODS OF GENE THERAPY FOR TREATMENT OF INHERITED EPIDERMOLYSIS BULLOSAБейлинА. К.BeilinA. K.

119334, г. Москва, ул. Вавилова, д. 26117997, г. Москва, ул. Островитянова, д. 1

аспирант, мл. науч. сотр. отдела регенеративной медицины

Тел.: 8-495-434-12-83

Vavilova ul. 26, 119334, Moscow

Ostrovitianov ul. 1, 117997, Moscow

arkadii.beilin@gmail.comГурскаяН. Г.GurskayaN. G.

119334, г. Москва, ул. Вавилова, д. 26

117997, г. Москва, ул. Островитянова, д. 1

канд. биол. наук, ст. науч. сотр. отдела регенеративной медицины

Тел: 8-495-434-12-83

Vavilova ul. 26, 119334, Moscow

Ostrovitianov ul. 1, 117997, Moscow

ngurskaya@mail.ruВоротелякЕ. А.VorotelyakE. A.

119334, г. Москва, ул. Вавилова, д. 26

117997, г. Москва, ул. Островитянова, д. 1

докт. биол. наук, чл.-корр. РАН, зав. отделом регенеративной медицины НИИ трансляционной медицины, зав. лабораторией клеточной биологии

Тел.: 8-499-135-40-81

Vavilova ul. 26, 119334, Moscow

Ostrovitianov ul. 1, 117997, Moscow

vorotelyak@yandex.ruИнститут биологии развития имени Н.К. Кольцова; Российский национальный исследовательский медицинский университет имени Н.И. Пирогова Минздрава РоссииРоссияKoltzov Institute of Developmental Biology, Russian Academy of Sciences; Pirogov Russian National Research Medical UniversityRussian Federation201829112018734233241Copyright © Бейлин А.К., Гурская Н.Г., Воротеляк Е.А., 20182018Бейлин А.К., Гурская Н.Г., Воротеляк Е.А.Beilin A.K., Gurskaya N.G., Vorotelyak E.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/656

Врожденный буллезный эпидермолиз (ВБЭ) – это гетерогенная группа редких генодерматозов, характеризующаяся повышенной “ранимостью” кожи, проявляющейся как образование пузырей и незаживающих эрозий на коже и слизистых оболочках внутренних органов при незначительных механических воздействиях. Выделяют три основных типа ВБЭ: простой, пограничный и дистрофический буллезные эпидермолизы, каждый из которых вызывается мутациями в генах, кодирующих соответственно белки эпидермиса, зоны базальной мембраны или дермы; отдельно выделяют – четвертый тип ВБЭ – гемидесмосомный или синдром Киндлер, при котором мутации повреждают ген FERMT1, кодирующий белок киндлин-1. Существующие подходы, призванные улучшить состояние больных ВБЭ, находятся на разных стадиях разработки: часть из них уже используют в клинике, для других еще проводятся лабораторные исследования. В зависимости от типа ВБЭ и характера наследования мутации применяются различные стратегии генетической терапии: от заместительной генной терапии с помощью вирусной экспрессии до редактирования генома с помощью программируемых синтетических нуклеаз. Накопленный опыт клеточной терапии по аллогенным и аутологическим пересадкам в сочетании с генной терапией позволяет создать новые подходы к функциональной терапии ВБЭ ex vivo.

Inherited epidermolysis bullosa (EB) is a heterogeneous group of rare genodermatoses with a high skin fragility manifested by the formation of destructive blisters and non-healing erosions on the skin and mucous membranes as a reaction to minor mechanical influences. There are three main types of EB: simple, junctional and dystrophic, each is caused by mutations in genes that encode epidermal, zones of the basement membrane or dermis proteins, respectively. The fourth type of EB is also described – hemidesmosomal or Kindler syndrome with impairments in kindlin-1 protein encoded by the FERMT1 gene. The existing ways to improve the living conditions of patients with EB are at different stages of development: some of them are already used in the clinic, while others are still under laboratory research. Various strategies are used, depending on the type of EB and the nature of mutation inheritance: from the functional gene replacement therapy based on the viral expression to the genome editing methods by programmable synthetic nucleases. The accumulated experience of allogeneic and autologous transplants of skin equivalents opens the prospect for using new approaches to functional gene and cell therapy ex vivo.

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