Innovative approaches to genome editing in the treatment of neurodegenerative diseases

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  • Authors: Tereshchenko S.Y.1, Potupchik T.V.2, Evert L.S.1,3, Kovalchuk V.A.4, Filippova M.A.4, Magalova A.R.5
  • Affiliations:
    1. Federal Research Center “Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences”
    2. Federal 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 Federation
    3. Khakass State University named after N.F. Katanov of the Ministry of Science and Higher Education of the Russian Federation, Medical Institute
    4. Federal State Budgetary Educational Institution of Higher Education “Yaroslavl State Medical University” of the Ministry of Health of the Russian Federation
    5. Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
  • Issue: Vol 22, No 6 (2024)
  • Pages: 29-39
  • Section: Reviews
  • URL: https://journals.eco-vector.com/1728-2918/article/view/677287
  • DOI: https://doi.org/10.29296/24999490-2024-06-04
  • ID: 677287

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Abstract

The purpose of this review is to analyze current advances in the field of genome editing, their application for the modeling and treatment of neurodegenerative diseases, as well as to discuss current limitations and prospects for overcoming barriers in clinical practice.

Materials and methods. To achieve this goal, a systematic analysis of literature over the past nine years (2016–2024) was conducted in the databases CyberLeninka, eLibrary, PubMed, Cochrane Library, SAGE Premier, Springer and Wiley Journals.

The main provisions. Neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases remain a serious challenge for modern medicine, characterized by progressive loss of neurons and the lack of effective therapeutic methods capable of stopping or reversing the pathological process. In recent years, genome editing technologies, including CRISPR-Cas9, TALEN and ZFN, have opened up new horizons in the treatment of these diseases. However, their clinical application is associated with a number of limitations, including problems of delivering editing tools to cells of the central nervous system, the risk of non-target mutations, and ethical issues. In this regard, the improvement of genome editing methods is one of the key areas. Modern methods such as CRISPR-Cas9, basic and prime editing, as well as epigenomic and RNA editing, have demonstrated high potential for accurate correction of genetic defects and modification of pathogenetic processes. Improvements in delivery systems, including viral and non-viral methods, have made it possible to overcome barriers such as low permeability of the blood-brain barrier and increase the effectiveness of therapy.

Conclusion. In recent years, significant progress has been made in the development of methods aimed at improving the safety of genomic editing in the nervous system. Despite significant advances, genome editing technologies face a number of challenges, including the need to increase specificity, minimize non-targeted effects, improve editing in postmitotic neurons and develop long-term safety monitoring methods, as well as address ethical issues related to the clinical application of these technologies.

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About the authors

Sergey Yuryevich Tereshchenko

Federal Research Center “Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences”

Author for correspondence.
Email: legise@mail.ru
ORCID iD: 0000-0002-1605-7859

Head of the Clinical Department of Somatic and Mental Health of Children, Research Institute of Medical Problems of the North, Doctor of Medical Sciences, Professor

Russian Federation, Partizan Zheleznyak str., 3G, Krasnoyarsk, 660022

Tatyana Vitalievna Potupchik

Federal 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 Federation

Email: potupchik_tatyana@mail.ru
ORCID iD: 0000-0003-1133-4447

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

Russian Federation, Partizan Zheleznyak str., 1, Krasnoyarsk, 660022

Lydia Semenovna Evert

Federal Research Center “Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences”; Khakass State University named after N.F. Katanov of the Ministry of Science and Higher Education of the Russian Federation, Medical Institute

Email: lidiya_evert@mail.ru
ORCID iD: 0000-0003-0665-7428

Chief Researcher of the Clinical Department of Somatic and Mental Health of Children, a separate unit – Research Institute of Medical Problems of the North, Professor of the Department of General Professional Disciplines, Medical Institute. Doctor of Medical Sciences.

Russian Federation, Partizan Zheleznyak str., 3G, Krasnoyarsk, 660022; Lenin Avenue, 90, Abakan, 655017

Vladimir Alekseevich Kovalchuk

Federal State Budgetary Educational Institution of Higher Education “Yaroslavl State Medical University” of the Ministry of Health of the Russian Federation

Email: ropegi47@gmail.com
ORCID iD: 0009-0005-5183-4499

6th year student

Russian Federation, Revolutsionnaya str., 5, Yaroslavl, Yaroslavl region, 150000

Maria Andreevna Filippova

Federal State Budgetary Educational Institution of Higher Education “Yaroslavl State Medical University” of the Ministry of Health of the Russian Federation

Email: mari.filippova.99@inbox.ru
ORCID iD: 0009-0008-3687-9404

6th year student

Russian Federation, Revolutsionnaya str., 5, Yaroslavl, Yaroslavl region, 150000

Aysun Renatovna Magalova

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: amagalova2001@mail.ru
ORCID iD: 0009-0007-0652-2212

6th year student

Russian Federation, Trubetskaya str., 8, build. 2, Moscow, 119048

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