vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-28vavilov-4094Research ArticleАКТУАЛЬНЫЕ ТЕХНОЛОГИИMAINSTREAM TECHNOLOGIESНевирусные системы внутриклеточной доставки инструментов редактирования геномаNon-viral systems for intracellular delivery of genome editing toolsШайхутдиновИ. Х.ShaikhutdinovI. H.

Самара

Samara

ИльясовП. В.IlyasovP. V.

Самара

Samara

p.v.ilyasov@samsmu.ruГрибковаО. В.GribkovaO. V.

Самара

Samara

ЛимареваЛ. В.LimarevaL.  V.

Самара

Samara

Самарский государственный медицинский университет Министерства здравоохранения Российской ФедерацииРоссияSamara State Medical University of the Ministry of Healthcare of the Russian FederationRussian Federation202411042024282239248Copyright © Шайхутдинов И.Х., Ильясов П.В., Грибкова О.В., Лимарева Л.В., 20242024Шайхутдинов И.Х., Ильясов П.В., Грибкова О.В., Лимарева Л.В.Shaikhutdinov I.H., Ilyasov P.V., Gribkova O.V., Limareva L.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4094

Последние десятилетия отмечены интенсивным развитием технологий и систем редактирования генов, которое вывело генную инженерию на новый уровень. Важным звеном этих технологий является специфичная и эффективная доставка компонентов таких систем в клетки-мишени. Традиционные векторы не всегда подходят для этой цели ввиду ограниченного объема полезной нагрузки, рисков, связанных с канцерогенезом и иммуногенностью, токсичности, необходимости высокой степени очистки и оценки качества полученных вирусных носителей, а также возможности встраивания вируса в геном хозяина, что может приводить к сверхэкспрессии компонентов вируса и проблемам с безопасностью. Это обусловливает актуальность поиска новых средств внутриклеточной доставки белков и нуклеиновых кислот. В данной работе приведен обзор абиотических векторов и систем доставки инструментов для редактирования генома, включая липосомы и твердые липидные наночастицы, мембранные везикулы иной природы, пептиды, проникающие в клетки, мицеллы, дендримеры, углеродные нанотрубки, неорганические, полимерные и другие наночастицы, металл-органические каркасные полимеры. Рассмотрены их преимущества, недостатки и предпочтительные области применения, а также возможность их использования для доставки систем редактирования генов. Особое внимание уделено металл-органическим каркасным полимерам и их потенциалу в качестве средств избирательной внутриклеточной доставки белков и полинуклеотидов. Сделан вывод о том, что дальнейшее развитие таких векторов и технологий на их основе может привести к появлению безопасных и эффективных систем доставки, способных длительно циркулировать в крови и распознавать клетки-мишени, обеспечивая адресное высвобождение полезной нагрузки в неизменном состоянии и тем самым улучшая результаты редактирования генов.

A hallmark of the last decades is an extensive development of genome editing systems and technologies propelling genetic engineering to the next level. Specific and efficient delivery of genome editing tools to target cells is one of the key elements of such technologies. Conventional vectors are not always suitable for this purpose due to a limited cargo volume, risks related to cancer and immune reactions, toxicity, a need for high-purity viral material and quality control, as well as a possibility of integration of the virus into the host genome leading to overexpression of the vector components and safety problems. Therefore, the search for novel approaches to delivering proteins and nucleic acids into cells is a relevant priority. This work reviews abiotic vectors and systems for delivering genome editing tools into target cells, including liposomes and solid lipid particles, other membrane-based vesicles, cell-penetrating peptides, micelles, dendrimers, carbon nanotubes, inorganic, polymer, metal and other nanoparticles. It considers advantages, drawbacks and preferred applications of such systems as well as suitability thereof for the delivery of genome editing systems. A particular emphasis is placed on metal-organic frameworks (MOFs) and their potential in the targeted intracellular delivery of proteins and polynucleotides. It has been concluded that further development of MOF-based vectors and technologies, as well as combining MOFs with other carriers can result in safe and efficient delivery systems, which would be able to circulate in the body for a long time while recognizing target cells and ensuring cell-specific delivery and release of intact cargoes and, thereby, improving the genome editing outcome. 

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