Проблемные аспекты разработки и регистрации генотерапевтических препаратов
https://doi.org/10.30895/2221-996X-2022-22-1-6-22
Резюме
В настоящее время известно большое количество заболеваний, патогенез которых обусловлен генетическими нарушениями. Достижения в области генетики и биотехнологии привели к созданию методов, которые позволяют получить практически любой ген, что в конечном счете привело к появлению нового класса лекарственных средств – генотерапевтических препаратов (ГТП). Цель работы – критический анализ международного опыта создания и регистрации генотерапевтических лекарственных препаратов. В обзоре освещены проблемы разработки ГТП, связанные с поиском оптимального подхода для доставки терапевтического гена в клетки-мишени. Обосновано, что перспективными средствами доставки генов являются вирусные векторы, среди которых наибольшей эффективностью и безопасностью обладают препараты на основе аденовируса (AV) и аденоассоциированного вируса (AAV). Рассмотрены современные подходы для генного редактирования, позволяющие модифицировать AV и AAV для повышения эффективности и безопасности ГТП. Данные модификации необходимы для включения в вирусный вектор терапевтического гена большого размера, снижения уровня экспрессии вирусных белков и снижения иммуногенности вирусного вектора. Представлен опыт регистрации ГТП в регуляторных органах США и Европейского союза, в том числе сведения о подкомитетах в структурах FDA и EMA, выполняющих рекомендательные функции. Отмечено, что в Российской Федерации зарегистрирован один ГТП отечественного производства и активно ведутся разработки других препаратов данной группы. Сделано заключение о необходимости формирования отечественной нормативной базы для разработки и регистрации ГТП, а также нормативных рекомендаций в рамках государств – членов Евразийского экономического союза.
Ключевые слова
Об авторах
А. А. СолдатовРоссия
Солдатов Александр Алексеевич, доктор медицинских наук
Петровский б-р, д. 8, стр. 2, Москва, 127051
Ж. И. Авдеева
Россия
Авдеева Жанна Ильдаровна, доктор медицинских наук, профессор
Петровский б-р, д. 8, стр. 2, Москва, 127051
Д. В. Горенков
Россия
Горенков Дмитрий Витальевич
Петровский б-р, д. 8, стр. 2, Москва, 127051
Л. М. Хантимирова
Россия
Хантимирова Лейсан Маратовна, кандидат биологических наук
Петровский б-р, д. 8, стр. 2, Москва, 127051
С. Г. Гусева
Россия
Гусева Светлана Геннадиевна
Петровский б-р, д. 8, стр. 2, Москва, 127051
В. А. Меркулов
Россия
Меркулов Вадим Анатольевич, доктор медицинских наук, профессор
Петровский б-р, д. 8, стр. 2, Москва, 127051
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Солдатов А.А., Авдеева Ж.И., Горенков Д.В., Хантимирова Л.М., Гусева С.Г., Меркулов В.А. Проблемные аспекты разработки и регистрации генотерапевтических препаратов. БИОпрепараты. Профилактика, диагностика, лечение. 2022;22(1):6-22. https://doi.org/10.30895/2221-996X-2022-22-1-6-22
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Soldatov A.A., Avdeeva Zh.I., Gorenkov D.V., Khantimirova L.M., Guseva S.G., Merkulov V.A. Challenges in development and authorisation of gene therapy products. Biological Products. Prevention, Diagnosis, Treatment. 2022;22(1):6-22. (In Russ.) https://doi.org/10.30895/2221-996X-2022-22-1-6-22