biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Products10.30895/2221-996X-2018-18-3-140-149biopreparat-169Research ArticleОБЗОРЫREVIEWSРедактирование генома и биомедицинские клеточные продукты: современное состояние, безопасность и эффективностьGenome-Editing and Biomedical Cell Products: Current State, Safety and Efficacyhttps://orcid.org/0000-0003-1620-6233ГоряевА. А.GoryaevA. A.

канд. биол. наук, заместитель начальника управления экспертизы противобактериальных МИБП Центра экспертизы и контроля МИБП ФГБУ «НЦЭСМП» Минздрава России

Candidate of Biological Sciences, Deputy Head of the Division for Expert Evaluation of Antibacterial Medicinal Immunobiological Products of the Centre for Evaluation and Control of Medicinal Immunobiological Products of the FSBI «SCEEMP» of the Ministry of Health of Russia

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

 

Goryaev@expmed.ruhttps://orcid.org/0000-0002-8527-2157СавкинаМ. В.SavkinaM. V.

канд. биол. наук, эксперт 1 категории управления экспертизы противобактериальных МИБП Центра экспертизы и контроля МИБП ФГБУ «НЦЭСМП» Минздрава России

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация 

Candidate of Biological Sciences, 1st Professional Category Expert of the Division  for Expert Evaluation of Antibacterial Medicinal Immunobiological Products of the Centre for Evaluation and Control of Medicinal Immunobiological Products of the FSBI «SCEEMP» of the Ministry of Health of Russia

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

 

https://orcid.org/0000-0003-1755-6649МефедК. М.MefedK. M.

канд. биол. наук, главный эксперт лаборатории вирусных вакцин Испытательного центра экспертизы качества МИБП ФГБУ «НЦЭСМП» Минздрава России

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация 

Candidate of Biological Sciences, Chief Expert of the Laboratory of Viral Vaccines of the Testing Centre for Evaluation of Medicinal Immunobiological Products’ Quality of the FSBI «SCEEMP» of the Ministry of Health of Russia

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

 

https://orcid.org/0000-0001-6472-6386БондаревВ. П.BondarevV. P.

д-р мед. наук, профессор, директор Центра экспертизы и контроля МИБП ФГБУ «НЦЭСМП» Минздрава России

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация 

Doctor of Medical Sciences, Professor, Director of the Centre for Evaluation and Control of Medicinal Immunobiological Products of the FSBI «SCEEMP» of the  Ministry of Health of Russia

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

 

https://orcid.org/0000-0003-4891-973XМеркуловВ. А.MerkulovV. A.

д-р мед. наук, профессор, заместитель генерального директора по экспертизе лекарственных средств ФГБУ «НЦЭСМП» Минздрава России

Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация 

Doctor of Medical Sciences, Professor, Deputy Director-General for Medicinal Products` Evaluation of the FSBI «SCEEMP» of the Ministry of Health of Russia

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

ТарасовВ. В.TarasovV. V.

канд. фарм. наук, доцент, директор Института фармации и трансляционной медицины ФГАОУ ВО Первый МГМУ им. И. М. Сеченова Минздрава России (Сеченовский Университет)

Candidate of Pharmaceutical Sciences, Assistant Professor, Director of the Institute of Pharmacy and Translational Medicine of FSAEI HE I.M. Sechenov First MSMU MOH Russia (Sechenovskiy University)

8/2 Trubetskaya St., Moscow 119991, Russian Federation

 

Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации.РоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian FederationФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования Первый Московский государственный медицинский университет им. И. М. Сеченова Министерства здравоохранения Российской ФедерацииРоссияI. M. Sechenov First Moscow State Medical UniversityRussian Federation201825092018183140149Copyright © Горяев А.А., Савкина М.В., Мефед К.М., Бондарев В.П., Меркулов В.А., Тарасов В.В., 20182018Горяев А.А., Савкина М.В., Мефед К.М., Бондарев В.П., Меркулов В.А., Тарасов В.В.Goryaev A.A., Savkina M.V., Mefed K.M., Bondarev V.P., Merkulov V.A., Tarasov V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.biopreparations.ru/jour/article/view/169

Успехи в технологиях ex vivo редактирования генома человека позволили разработать новые подходы в лечении генетических, экологических, инфекционных и других заболеваний, в том числе с использованием биомедицинских клеточных продуктов. Но, несмотря на быстрое развитие данных технологий и большое количество проводимых клинических исследований во многих странах мира, только 4 препарата (Strimvelis, Zalmoxis, Kymriah и Yescarta), содержащие ex vivo генно-модифицированные клетки человека, разрешены к применению в странах Европейского союза и США. В данной работе рассмотрены три перспективные технологии (ZFN, TALEN и CRISPR), позволяющие легко и эффективно проводить редактирование генома в необходимых сайтах, тем самым создавая платформу для дальнейшего развития генной инженерии клеток человека. Описана технология получения химерных антигенных рецепторов (CAR). Также приведены сведения об эффективности и безопасности одобренных препаратов: Strimvelis, содержащего аутологичные CD34+-клетки, ex vivo трансдуцированные ретровирусным вектором с геном аденозиндезаминазы, Zalmoxis, содержащего модифицированные аллогенные Т-клетки, а также двух препаратов Kymriah и Yescarta, содержащих аутологичные T-клетки с химерными антигенными рецепторами к антигену CD19, предназначенных для лечения CD19+ гематологических злокачественных новообразований.

Advances in ex vivo technologies of human genome editing have made it possible to develop new approaches to the treatment of genetic, oncological, infectious and other diseases, which may involve the use of biomedical cell products. However, despite the rapid development of these technologies and a large number of clinical trials conducted in many countries around the world, only 4 products (Strimvelis, Zalmoxis, Kymriah and Yescarta) containing ex vivo genetically modified human cells are authorised for use in the European Union and the United States of America. This paper considers three promising technologies (ZFN, TALEN and CRISPR) that allow for easy and effective editing of the genome at the sites of interest, thereby creating a platform for further development of the genetic engineering of human cells. It describes the technology of engineering chimeric antigen receptors (CARs). It also provides data on the efficacy and safety of the approved products: Strimvelis which contains autologous CD34+ cells transduced ex vivo with a retroviral vector containing adenosine deaminase gene, Zalmoxis which contains modified allogeneic T-cells, and two products: Kymriah and Yescarta which contain autologous T-cells with CARs to CD19 antigen, intended for the treatment of CD19+ hematological malignancies.

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