Molekulyarnaya Meditsina (Molecular medicine)Molekulyarnaya Meditsina (Molecular medicine)Молекулярная медицина1728-29182499-9490Russkiy Vrach Publishing House67867210.29296/24999490-2025-02-03ReviewsОбзорыReview ArticleGenome editing in neurodegenerative diseases: risk analysis, technological challenges, and prospects for clinical applicationРедактирование генома при нейродегенеративных заболеваниях: анализ рисков, технологические вызовы и перспективы клинического примененияhttps://orcid.org/0000-0003-0665-7428EvertLydia SemenovnaЭвертЛидия Семеновна
Russian Federation

Scientific Research Institute of Medical Problems of the North, Chief Researcher, Clinical Department of Somatic and Mental Health of Children, Medical Institute, Doctor of Medical Sciences

Научно-исследовательский институт медицинских проблем Севера, главный научный сотрудник клинического отделения соматического и психического здоровья детей, Медицинский институт, Доктор медицинских наук

lidiya_evert@mail.ruhttps://orcid.org/0000-0003-1133-4447PotupchikTatyana VitalievnaПотупчикТатьяна Витальевна
Russian Federation

Associate Professor, Department of Pharmacology and Clinical Pharmacology with a postgraduate course, Candidate of Medical Sciences

доцент кафедры фармакологии и клинической фармакологии с курсом постдипломного образования, кандидат медицинских наук

potupchik_tatyana@mail.ruhttps://orcid.org/0000-0002-6126-665XVeselovaOlga FedorovnaВеселоваОльга Федоровна
Russian Federation

Head of the Department of Pharmacology and Clinical Pharmacology with a postgraduate course, Candidate of Medical Sciences

заведующая кафедрой фармакологии и клинической фармакологии с курсом постдипломного образования, Кандидат медицинских наук

Veselovaof@mail.ruhttps://orcid.org/0009-0005-7622-2827SvetlakovaIrina SergeevnaСветлаковаИрина Сергеевна
Russian Federation

6th year student

студент VI курса

irinasvetlakova2000@gmail.ruhttps://orcid.org/0009-0001-2122-8501PanchenkoViktor AndreevichПанченкоВиктор Андреевич
Russian Federation

6th year student

студент VI курса

viktor-panchenko@inbox.ruhttps://orcid.org/0009-0001-7884-4209KuzhashevaRina RasimovnaКужашеваРина Расимовна
Russian Federation

6th year student

студент VI курса

rkuzhasheva@bk.ruhttps://orcid.org/0009-0006-6084-2578MelnikovaAnastasia NikolaevnaМельниковаАнастасия Николаевна
Russian Federation

doctor of the emergency department

врач приемного отделения

nasmel00@mail.ruFederal Research Center “Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences”Федеральный исследовательский центр «Красноярский научный центр Сибирского отделения Российской академии наук»Khakass State University named after N.F. Katanov of the Ministry of Science and Higher Education of the Russian FederationХакасский государственный университет имени Н.Ф. Катанова Министерства науки и высшего образования РФFederal State Budgetary Educational Institution of Higher Education “Krasnoyarsk State Medical University named after Professor V.F. Voino-Yasenetsky” of the Ministry of Health of the Russian FederationФГБОУ ВО «Красноярский государственный медицинский университет имени профессора В.Ф. Войно-Ясенецкого» Министерства здравоохранения Российской ФедерацииFederal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет им.и Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииFederal State Budgetary Educational Institution of Higher Education “Bashkir State Medical University” of the Ministry of Health of the Russian FederationФГБОУ ВО «Башкирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииRegional Budgetary Healthcare Institution “Zolotukhinskaya Central District Hospital”Областное бюджетное учреждение здравоохранения «Золотухинская центральная районная больница»2004202523221311704202517042025Copyright ©; 2025, Russkiy Vrach Publishing HouseCopyright ©; 2025, ИД "Русский врач"2025Russkiy Vrach Publishing HouseИД "Русский врач"https://journals.eco-vector.com/1728-2918/article/view/678672

Objective. To analyze the potential risks and technological limitations of using genome editing methods in neurodegenerative diseases, as well as to assess the prospects for their implementation in clinical practice.

Material and methods. A systematic analysis of the literature for the period 2014–2024 in the databases PubMed, Cochrane Library, ClinicalTrials.gov, SAGE Premier, Springer and Wiley Journals. The key risks of using genome editing technologies are considered, including inappropriate effects, immunological reactions, and long-term consequences of changes in the DNA of nervous tissue.

Results. The main technological limitations are analyzed, including problems of delivery across the blood-brain barrier, low editing efficiency in postmitotic neurons, and the complexity of long-term expression of components of editing systems. The prospects of introducing technologies into clinical practice are assessed, taking into account the current regulatory landscape in various countries.

Conclusion. Despite significant technological challenges and potential risks, the development of genome editing techniques opens up prospects for the creation of effective treatments for neurodegenerative diseases. Key areas of further research include improving the safety and specificity of editing, optimizing delivery systems, and developing methods for long-term monitoring of the effects of genetic modifications in the nervous system.

Цель исследования. Проанализировать потенциальные риски и технологические ограничения применения методов редактирования генома при нейродегенеративных заболеваниях, а также оценить перспективы их внедрения в клиническую практику.

Материал и методы. Проведен систематический анализ литературы за период 2014–2024 гг. в базах данных PubMed, Cochrane Library, ClinicalTrials.gov, SAGE Premier, Springer и Wiley Journals. Рассмотрены ключевые риски применения технологий редактирования генома, включая нецелевые эффекты, иммунологические реакции и долгосрочные последствия изменений в ДНК нервной ткани.

Результаты. Проанализированы основные технологические ограничения, в том числе проблемы доставки через гематоэнцефалический барьер, низкая эффективность редактирования в постмитотических нейронах и сложности долгосрочной экспрессии компонентов систем редактирования. Оценены перспективы внедрения технологий в клиническую практику с учетом текущего регуляторного ландшафта в различных странах.

Заключение. Несмотря на существенные технологические вызовы и потенциальные риски, развитие методов редактирования генома открывает перспективы для создания эффективных методов лечения нейродегенеративных заболеваний. Ключевыми направлениями дальнейших исследований являются повышение безопасности и специфичности редактирования, оптимизация систем доставки и разработка методов долгосрочного мониторинга последствий генетических модификаций в нервной системе.

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