uzakuescУченые записки Казанского университета. Серия Естественные наукиUchenye Zapiski Kazanskogo Universiteta Seriya Estestvennye Nauki2542-064X2500-218XKazan (Volga Region) Federal University10.26907/2542-064X.2024.4.683-703uzakuesc-200Research ArticleСтатьиАнализ биораспределения аденоассоциированных вирусов 9 и rh.10 серотипов, кодирующих ген арилсульфатазы А, после предварительной иммунизации свиней вирусом 9 серотипаBiodistribution Analysis of Adeno-Associated Viral Vectors of Serotypes 9 and rh.10 Encoding Arylsulfatase A Following Prior Immunization with Serotype 9 in PigsМуллагуловаА. И.MullagulovaA. I.

Муллагулова Айсылу Илдаровна, аспирант кафедры генетики Института фундаментальной медицины и биологии, младший научный сотрудник НИЛ OpenLab Генные и клеточные технологии Научно-клинического центра прецизионной и регенеративной медицины Института фундаментальной медицины и биологии

ул. Кремлевская, д. 18, г. Казань, 420008

Kazan, 420008 

aisilu.mullagulova@yandex.ruШаймардановаА. А.ShaimardanovaA. A.

Шаймарданова Алиса Алмазовна, кандидат биологических наук, научный сотрудник НИЛ OpenLab Генные и клеточные технологии Научно-клинического центра прецизионной и регенеративной медицины Института фундаментальной медицины и биологии

ул. Кремлевская, д. 18, г. Казань, 420008

Kazan, 420008 

aliceshaimardanova@mail.ruМухамедшинаЯ. О.MukhamedshinaYa. O.

Мухамедшина Яна Олеговна, доктор медицинских наук, доцент, ведущий научный сотрудник НИЛ OpenLab Генные и клеточные технологии Научно-клинического центра прецизионной и регенеративной медицины Института фундаментальной медицины и биологии; главный научный сотрудник

ул. Кремлевская, д. 18, г. Казань, 420008

Оренбургский тракт, д. 138., г. Казань, 420064

Kazan, 420008 

Kazan, 420064 

СоловьеваВ. В.SolovyevaV. V.

Соловьева Валерия Владимировна, кандидат биологических наук, доцент, ведущий научный сотрудник НИЛ OpenLab Генные и клеточные технологии Научно-клинического центра прецизионной и регенеративной медицины Института фундаментальной медицины и биологии

ул. Кремлевская, д. 18, г. Казань, 420008

Kazan, 420008 

solovyovavv@gmail.comИбрахимА.IbrahimA.

Ибрахим Ахмад, магистрант кафедры генетики Института фундаментальной медицины и биологии

ул. Кремлевская, д. 18, г. Казань, 420008

Kazan, 420008 

ahmadibrahim4949@gmail.comРизвановА. А.RizvanovA. A.

Ризванов Альберт Анатольевич, доктор биологических наук, профессор, главный научный сотрудник НИЛ OpenLab Генные и клеточные технологии Научно-клинического центра прецизионной и регенеративной медицины, профессор кафедры генетики Института фундаментальной медицины и биологии; академик-секретарь отделения медицинских и биологических наук

ул. Кремлевская, д. 18, г. Казань, 420008

Бауманa, д. 20, г. Казань, 420111

Kazan, 420008

Kazan, 420111 

rizvanov@gmail.comКазанский (Приволжский) федеральный университетРоссияKazan Federal UniversityRussian FederationКазанский (Приволжский) федеральный университет; Республиканская клиническая больницаРоссияKazan Federal University; Republican Clinical Hospital of TatarstanRussian FederationКазанский (Приволжский) федеральный университет; Академия наук Республики ТатарстанРоссияKazan Federal University; Tatarstan Academy of SciencesRussian Federation2024261120241664683–703Copyright © Муллагулова А.И., Шаймарданова А.А., Мухамедшина Я.О., Соловьева В.В., Ибрахим А., Ризванов А.А., 20242024Муллагулова А.И., Шаймарданова А.А., Мухамедшина Я.О., Соловьева В.В., Ибрахим А., Ризванов А.А.Mullagulova A.I., Shaimardanova A.A., Mukhamedshina Y.O., Solovyeva V.V., Ibrahim A., Rizvanov A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://uzakuesc.elpub.ru/jour/article/view/200

Лизосомные болезни накопления представляют собой наследственные заболевания, связанные с нарушением функции лизосом, включая работу ферментов, важных для клеточного метаболизма, сигнальных путей и других биологических процессов. Метахроматическая лейкодистрофия (МЛД), входящая в группу лизосомных болезней накопления, вызвана дефицитом арилсульфатазы А (ARSA), что приводит к накоплению сульфатидов и разрушению миелиновых оболочек структур нервной системы. В статье обсуждается эффективность использования аденоассоциированных вирусов (AAВ) при нейродегенеративных заболеваниях, включая МЛД. Показано биораспределение и безопасность векторов AAВ9-ARSA и AAВrh.10-ARSA после предварительной иммунизации свиней. Обсуждены иммунные аспекты, связанные с генной терапией на основе AAВ, а также возможные ограничения в эффективности и долгосрочности такой терапии.

Lysosomal storage diseases are a group of inherited disorders caused by lysosomal dysfunction, impairing cellular metabolic enzymes, signaling pathways, and other biological processes. Among them is metachromatic leukodystrophy (MLD) associated with arylsulfatase A (ARSA) deficiency, which leads to the accumulation of sulfatides and the destruction of myelin sheaths in the nervous system. This study evaluates the therapeutic efficacy of adeno-associated viruses (AAVs) in treating neurodegenerative diseases such as MLD. The biodistribution and safety of AAV9-ARSA and AAVrh.10-ARSA vectors following prior immunization in pigs were shown. The immune aspects of AAV-based gene therapy were outlined. Its potential efficacy and durability limitations were discussed.

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