oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2024-23-4-152-161oncotomsk-3201Research ArticleОБЗОРЫREVIEWSГенная инженерия в онкологии, основанная на технологии CRISPR-Cas9Genetic engineering in oncology based on CRISPR-Cas9 technologyhttps://orcid.org/0000-0001-8128-2553ПолатоваД. Ш.PolatovaD. Sh.

Полатова Джамила Шагайратовна, доктор медицинских наук, профессор кафедры онкологии и медицинской радиологии; директор

Author ID (Scopus): 57499570400

100115, г. Ташкент, ул. Арнасай, 28

100047, г. Ташкент, ул. Махтумкули, 103

Djamila Sh. Polatova, MD, DSc, Professor, Department of Oncology and Medical Radiology;  Director, Republican Center for Pediatric Oncology

Author ID (Scopus): 57499570400

28, Arnasay St., Tashkent, 100115

103, Makhtumkuli St., Tashkent

https://orcid.org/0000-0003-0064-3746МадаминовА. Ю.MadaminovA. Yu.

Мадаминов Ахмад Юлдашевич, ассистент кафедры онкологии и медицинской радиологии

Author ID (Scopus): 57232171600

100047, г. Ташкент, ул. Махтумкули, 103

Akhmad Yu. Madaminov, MD, Assistant, Department of Oncology and Medical Radiology

Author ID (Scopus): 57232171600

103, Makhtumkuli St., Tashkent

akhmad.madaminov@inbox.ruhttps://orcid.org/0000-0002-3416-5837СавкинА. В.SavkinA. V.

Савкин Александр Владимирович, кандидат медицинских наук, ассистент кафедры онкологии и медицинской радиологии

Author ID (Scopus): 57313093300

100047, г. Ташкент, ул. Махтумкули, 103

Alexander V. Savkin, MD, PhD, Assistant, Department of Oncology and Medical Radiology

 Author ID (Scopus): 57313093300

103, Makhtumkuli St., Tashkent

https://orcid.org/0009-0000-4488-7270ИбрагимоваД. А.IbragimovaD. A.

Ибрагимова Дилором Абдулазизовна, ассистент кафедры онкологии и медицинской радиологии

Author ID (Scopus): 58642429400

100047, г. Ташкент, ул. Махтумкули, 103

Dilorom A. Ibragimova, MD, Assistant, Department of Oncology and Medical Radiology

Author ID (Scopus): 58642429400

103, Makhtumkuli St., Tashkent

Республиканский центр детской онкологии, гематологии и клинической иммунологии; Ташкентский государственный стоматологический институтУзбекистанRepublican Center for Pediatric Oncology, Hematology and Clinical Immunology; Tashkent State Dental InstituteUzbekistanТашкентский государственный стоматологический институтУзбекистанTashkent State Dental InstituteUzbekistan202409092024234152161Copyright © Полатова Д.Ш., Мадаминов А.Ю., Савкин А.В., Ибрагимова Д.А., 20242024Полатова Д.Ш., Мадаминов А.Ю., Савкин А.В., Ибрагимова Д.А.Polatova D.S., Madaminov A.Y., Savkin A.V., Ibragimova D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/3201

Цель исследования – анализ современных научных данных, посвященных молекулярным механизмам системы CRISPR-Сas9 в редактировании генов, преимуществам и недостаткам в исследованиях рака и разработке новых методов лечения. Материал и методы. Комплексный электронный поиск соответствующих публикаций проведен в научных базах данных PubMed/MEDLINE, ScienceDirect, Wiley и Google Scholar за период с 2014 по 2024 г. Поиск был адаптирован к конкретным требованиям каждой базы данных на основе следующих ключевых слов: CRISPR-Cas9, sgРНК, редактирование генома, иммунотерапия рака, CAR-T. В результате поиска было найдено 487 публикаций по интересующей теме, из которых 54 были использованы для написания литературного обзора. Кроме того, в статье дискретно подчеркиваются важность и проблемы CRISPR-Cas9 при производстве генно-инженерных Т-клеток для их потенциального использования при лечении определенных типов рака. Результаты. CAR-T (Т-клетка с химерным антигенным рецептором)-терапия широко используется в качестве одного из основных компонентов иммунотерапии при лечении лейкемии, лимфомы и некоторых солидных опухолей. Разработка запрограммированных направляющих РНК (sgРНК) и новых модификаций белка Cas9 позволила сделать технологию гибкой и универсальной. CRISPR-Cas9 часто используется для модификации Т- и NK-клеток с помощью конструкции антигенных рецепторов для улучшения их сенсорных цепей сложной функциональности, способных распознавать и уничтожать опухолевые клетки. При этом доставка готового рибонуклеопротеинового (Cas9+sgРНК) комплекса в клетку позволяет избежать конститутивных процессов транскрипции и трансляции, что обеспечивает максимально быстрое редактирование генов. Заключение. В обзоре рассмотрены научные данные, подчеркивающие многообещающее влияние технологий CRISPR на исследования и лечение рака. CRISPR-Cas9 считается уникальной и эффективной технологией в области генной и биомолекулярной инженерии.

Purpose of the study: analysis of modern scientific data on the molecular mechanisms of the CRISPR-Cas9 system in gene editing, advantages and disadvantages in cancer research and the development of new treatment methods. Material and Methods. A comprehensive electronic search of relevant published studies was conducted in the scientific databases PubMed/MEDLINE, ScienceDirect, Wiley and Google Scholar published between 2014 and 2024. The search was tailored to the specific requirements of each database based on the following keywords: CRISPR-Cas9, sgRNA, genome editing, cancer immunotherapy, CAR-T. The search yielded 487 studies on the topic of interest, of which 54 were used to write the literature review. Additionally, the article discretely highlights the importance and challenges of CRISPR-Cas9 in the production of genetically engineered T cells for potential use in treating certain types of cancer. Results. Accordingly, CAR-T (chimeric antigen receptor T-cell) therapy is widely used as one of the main components of immunotherapy in the treatment of leukemia, lymphoma and some solid tumors. The development of programmed single guide RNAs (sgRNAs) and new modifications of the Cas9 protein has made the technology flexible and universal. CRISPR-Cas9 is often used to modify T and NK cells by designing antigen receptors to improve their sensory circuits with complex functionality capable of recognizing and killing tumor cells. At the same time, delivery of the finished ribonucleoprotein (Cas9+sgRNA) complex into the cell avoids the constitutive processes of transcription and translation, which ensures the fastest possible gene editing. Conclusion. In this review, we reviewed the scientific evidence highlighting the promising impact of CRISPR technologies in cancer research and treatment. CRISPR-Cas9 is considered a unique and effective technology in the field of genetic and biomolecular engineering.

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