Laboratory of Genome Editing

115522, Moscow, Moskvorechye str., 1, 3rd floor (rooms 306, 308-312, 314, 316)

Phones: +7 (499) 324-3579, +7 (499) 612-9989

The Laboratory of Genome Editing was organized on January 1, 2019 as a result of the separation of the genome editing group from the Laboratory of Mutagenesis.

The laboratory's efforts are focused on the topic of genome editing, including fundamental research for increasing the level of homologous recombination in CRISPR/Cas9 method, as well as applied research to develop treatment of hereditary monogenic diseases. The following works are carried out in the laboratory: 1) editing the most frequent mutation F508del in CFTR gene for the treatment of cystic fibrosis; 2) editing mutations for the treatment of hereditary forms of myopathies (dysferlinopathies, desminopathies); 3) editing of mutations in Glycogen storage disease type 1a. The laboratory uses the entire modern arsenal of genome editors, including the latest methods – base editors and prime editing.

Cystic fibrosis is one of the most common monogenic diseases. The electrolyte composition in the extracellular medium is disturbed due to mutations in the gene of the channel protein for chlorine ions (CFTR), so results to disruption of many organs. Pulmonary symptoms are dominant clinical features. Lungs’ pathology determines the prognosis and survival of the patients. Etiology-based therapy of this disease does not exist. Developed technologies of highly efficient target genome editing allow us to hope that such therapy will be worked out in the near future for many hereditary diseases. Using the technology of targeted nucleases CRISPR/Cas9, we are developing a method for correcting the most frequent mutation p.F508del in cystic fibrosis.

SELECTED PUBLICATIONS

1. Voldgorn YI, Adilgereeva EP, Nekrasov ED, Lavrov AV. Cultivation and Differentiation Change Nuclear Localization of Chromosome Centromeres in Human Mesenchymal Stem Cells. PLoS ONE, 2015, 10(3): e0118350. doi: 10.1371/journal.pone.0118350 http://dx.plos.org/10.1371/journal.pone.0118350
2. Lavrov A.V., Chelysheva E.Y., Smirnikhina S.A., Shukhov O.A., Turkina A.G., Adilgereeva E.P., Kutsev S.I. Frequent variations in cancer-related genes may play prognostic role in treatment of patients with chronic myeloid leukemia. BMC Genetics, 2016, 17(Suppl 1):14, DOI: 10.1186/s12863-015-0308-7 http://bmcgenet.biomedcentral.com/articles/10.1186/s12863-015-0308-7
3. Smirnikhina S.A., Lavrov A.V., Chelysheva E.Yu., Adilgereeva E.P., Shukhov O.A., Turkina A.G., Kutsev S.I. Whole-exome sequencing reveals potential molecular predictors of relapse after discontinuation of the targeted therapy in CML. Leukemia and Lymphoma, 2016, DOI: 10.3109/10428194.2015.1132420 http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1132420
4. Lavrov AV, Ustaeva OA, Adilgereeva EP, Smirnikhina SA, Chelysheva EY, Shukhov OA, Shatokhin YV, Mordanov SV, Turkina AG, Kutsev SI. Copy number variation analysis in cytochromes and glutathione S-transferases may predict efficacy of tyrosine kinase inhibitors in chronic myeloid leukemia. PLoS ONE, 2017 12(9):e0182901. https://doi.org/10.1371/journal.pone.0182901. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182901
5. Smirnikhina SA, Chelysheva EY, Lavrov AV, Kochergin-Nikitsky KS, Mozgovoy IV, Adilgereeva EP, Shukhov OA, Petrova AN, Bykova AV, Abdullaev AO, Turkina AG, Kutsev SI. Genetic markers of stable molecular remission in chronic myeloid leukemia after targeted therapy discontinuation. Leuk Lymphoma. 2018 Feb 9:1-4. doi: 10.1080/10428194.2018.1434880. https://www.tandfonline.com/doi/abs/10.1080/10428194.2018.1434880?journalCode=ilal20
6. Yakushina V.D., Lerner L.V., Lavrov A.V. Gene fusions in thyroid cancer. Thyroid. February 2018, 28(2): 158-167. https://doi.org/10.1089/thy.2017.0318
7. Smirnikhina SA, Anuchina AA., Lavrov AV. Ways of improving precise knock-in by genome editing technologies. Human Genetics, 2018, Hum Genet. 2019 Jan;138(1):1-19. doi: 10.1007/s00439-018-1953-5. https://link.springer.com/article/10.1007%2Fs00439-018-1953-5
8. Lavrov AV, Chelysheva EYu, Adilgereeva EP, Shukhov OA, Smirnikhina SA, Kochergin-Nikitsky KS, Yakushina VD, Tsaur GA, Mordanov SV, Turkina AG, Kutsev SI. Exome, transcriptome and miRNA analysis don’t reveal any molecular markers of TKI efficacy in primary CML patients. BMC Medical Genomics, 2019, doi: 10.1186/s12920-019-0481-z. https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-019-0481-z
9. Hsieh TC, Mensah MA, Pantel JT, Aguilar D, Bar O, Bayat A, Becerra-Solano L, Bentzen HB, Biskup S, Borisov O, Braaten O, Ciaccio C, Coutelier M, Cremer K, Danyel M, Daschkey S, Eden HD, Devriendt K, Wilson S, Douzgou S, Đukić D, Ehmke N, Fauth C, Fischer-Zirnsak B, Fleischer N, Gabriel H, Graul-Neumann L, Gripp KW, Gurovich Y, Gusina A, Haddad N, Hajjir N, Hanani Y, Hertzberg J, Hoertnagel K, Howell J, Ivanovski I, Kaindl A, Kamphans T, Kamphausen S, Karimov C, Kathom H, Keryan A, Knaus A, Köhler S, Kornak U, Lavrov A, Leitheiser M, Lyon GJ, Mangold E, Reina PM, Carrascal AM, Mitter D, Herrador LM, Nadav G, Nöthen M, Orrico A, Ott CE, Park K, Peterlin B, Pölsler L, Raas-Rothschild A, Randolph L, Revencu N, Fagerberg CR, Robinson PN, Rosnev S, Rudnik S, Rudolf G, Schatz U, Schossig A, Schubach M, Shanoon O, Sheridan E, Smirin-Yosef P, Spielmann M, Suk EK, Sznajer Y, Thiel CT, Thiel G, Verloes A, Vrecar I, Wahl D, Weber I, Winter K, Wiśniewska M, Wollnik B, Yeung MW, Zhao M, Zhu N, Zschocke J, Mundlos S, Horn D, Krawitz PM. PEDIA: prioritization of exome data by image analysis. Genet Med. 2019 Jun 5. doi: 10.1038/s41436-019-0566-2. [Epub ahead of print] https://www.nature.com/articles/s41436-019-0566-2
10. Anuchina A.A., Lavrov A.V., Smirnikhina S.A. TIRR: a potential front runner in HDR race − hypotheses and perspectives. Molecular Biology Reports, 2020. https://link.springer.com/article/10.1007/s11033-020-05285-x
11. Lavrov AV, Varenikov GG, Skoblov MYu. Genome scale analysis of pathogenic variants targetable for single base editing. BMC Medical Genomics. DOI: 10.1186/s12920-020-00735-8. https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-020-00735-8
12. Kondrateva E, Adilgereeva E, Amelina E, Tabakov V, Demchenko A, Ustinov K, Yasinovsky M, Voronina E, Lavrov A, Smirnikhina S. Generation of induced pluripotent stem cell line (RCMGi001-A) from human skin fibroblasts of a cystic fibrosis patient with p.F508del mutation. Stem Cell Research, 2020, Volume 48, October 2020, 101933, doi: 10.1016/j.scr.2020.101933 https://www.sciencedirect.com/science/article/pii/S1873506120302348
13. Kondrateva E., Demchenko A., Lavrov A., Smirnikhina S. An overview of currently available molecular Cas-tools for precise genome modification. Gene, 2020, 145225, 10.1016/j.gene.2020.145225. https://www.sciencedirect.com/science/article/pii/S0378111920308945
14. Smirnikhina SA. Prime Editing: Making the Move to Prime Time. The CRISPR Journal, 2020, Vol 3, N 5, p. 319-321. DOI: 10.1089/crispr.2020.29105.sas. https://www.liebertpub.com/doi/full/10.1089/crispr.2020.29105.sas
15. Smirnikhina SA, Kondrateva EV, Adilgereeva EP, Anuchina AA, Zaynitdinova MI, Slesarenko YaS., Ershova AS, Ustinov KD, Yasinovsky MI, Amelina EL, Voronina ES, Yakushina VD, Tabakov VYu, Lavrov AV. P.F508del editing in cells from cystic fibrosis patients. PLoS ONE 15(11): e0242094. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242094
16. Kondrateva E, Demchenko A, Slesarenko Y, Pozhitnova V, Yasinovsky M, Amelina E, Tabakov V, Voronina E, Lavrov A, Smirnikhina S. Generation of two induced pluripotent stem cell lines (RCMGi004-A and -B) from human skin fibroblasts of a cystic fibrosis patient with compound heterozygous F508del/W1282X mutations. Stem Cell Research, 2021, Volume 52, April 2021, 102232. DOI: 10.1016/j.scr.2021.102232. https://www.sciencedirect.com/science/article/pii/S1873506121000787?via%3Dihub
17. Kondrateva E., Demchenko A., Slesarenko Y., Yasinovsky M., Amelina E., Tabakov V., Voronina E., Lavrov A., Smirnikhina S. Derivation of iPSC line (RCMGi002-A) from dermal fibroblasts of a cystic fibrosis female patient with homozygous F508del mutation. Stem Cell Research, 2021, Volume 53, May 2021, 102251, DOI: 10.1016/j.scr.2021.102251. https://www.sciencedirect.com/science/article/pii/S1873506121000970?via%3Dihub
18. Kochergin-Nikitsky K, Belova L, Lavrov A, Smirnikhina S. Tissue and cell-type-specific transduction using rAAV vectors in lung diseases. J Mol Med (Berl). 2021 Aug;99(8):1057-1071. doi: 10.1007/s00109-021-02086-y. Epub 2021 May 21. PMID: 34021360. https://link.springer.com/article/10.1007%2Fs00109-021-02086-y
19. Zaynitdinova MI, Lavrov AV, Smirnikhina SA. Animal models for researching approaches to therapy of Duchenne muscular dystrophy. Transgenic Res. 2021 Aug 18. doi: 10.1007/s11248-021-00278-3. Epub ahead of print. PMID: 34409525. https://link.springer.com/article/10.1007%2Fs11248-021-00278-3
20. Slesarenko YS, Lavrov AV, Smirnikhina SA. Off-target effects of base editors: what we know and how we can reduce it. Curr Genet. 2021 Sep 13. doi: 10.1007/s00294-021-01211-1. Epub ahead of print. PMID: 34515826. https://link.springer.com/article/10.1007/s00294-021-01211-1
21. Polla DL, Fard MAF, Tabatabaei Z, Habibzadeh P, Levchenko OA, et al. Biallelic variants in TMEM222 cause a new autosomal recessive neurodevelopmental disorder. Genetics in Medicine, 2021, https://doi.org/10.1038/s41436-021-01133-w. https://www.nature.com/articles/s41436-021-01133-w
22. Voisin N, Schnur RE, Douzgou S, et al. Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy. Am J Hum Genet. 2021;108(5):857-873. doi:10.1016/j.ajhg.2021.04.001. https://www.sciencedirect.com/science/article/pii/S0002929721001324?via%3Dihub

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   https://iz.ru/1050551/anna-urmantceva/byk-praroditel-gennye-inzhenery-sozdali-adama-dlia-muzhskogo-stada
2. Коммерсантъ. 07.10.2020. «Генетические ножницы» взяли Нобелевку.
   https://www.kommersant.ru/doc/4521285#id1958196
3. «Эксперт» №44 (1182). 26.10.2020. Человек отредактированный.
   https://expert.ru/expert/2020/44/chelovek-otredaktirovannyij/
4. Агентство городских новостей Москва. 23.07.2020. Работа Медико-генетического научного центра имени академика Бочкова.
   https://www.mskagency.ru/materials/3025615
5. Минобрнауки. 28.07.2020. Российские ученые разрабатывают метод геномного редактирования для лечения пациентов с муковисцидозом.
   https://www.minobrnauki.gov.ru/ru/press-center/card/?id_4=2869
6. РИА новости. 22.10.2020 Спасет от рака. Кого будут лечить методом, отмеченным Нобелевской премией.​​​​​​​https://ria.ru/20201022/nobelevka-1580781340.html
7. ТАСС Наука. 19.11.2020. Потенциальная методика для лечения муковисцидоза оказалась высокоэффективной.
   https://nauka.tass.ru/nauka/10046151
8. Российский научный фонд. 20.11.2020. Приводящую к муковисцидозу мутацию удалось исправить в 5% клеток.
   https://rscf.ru/news/presidential-program/gennoy-terapii-dlya-lecheniya-mukovistsidoza/
9. Такие дела. 22.11.2020. Российские ученые с помощью геномного редактора исправили мутацию, вызывающую муковисцидоз. https://takiedela.ru/news/2020/11/22/redaktor-mukoviscidoz/
10. Медвестник. 22.11.2020. Российские ученые добились успеха в лечении муковисцидоза с помощью генной инженерии. https://medvestnik.ru/content/news/Uchenye-dobilis-uspeha-v-lechenii-mukoviscidoza-s-pomoshu-gennoi-injenerii.html
11. Indicator. 22.11.2020. Приводящую к муковисцидозу мутацию удалось исправить в 5% клеток. https://indicator.ru/medicine/privodyashuyu-k-mukoviscidozu-mutaciyu-udalos-ispravit-v-5-kletok-22-11-2020.htm
12. Пресс-центр ФГБНУ «МГНЦ». 28.11.2020. Исправить мутацию, приводящую к муковисцидозу, удалось в пяти процентах клеток. https://genetics-info.ru/news/ispravit-mutatsiyu-privodyashchuyu-k-mukovistsidozu-udalos-v-pyati-protsentakh-kletok/
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16. 31.03.2021 Ольга Левченко. Генетик: ученый или врач
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17. 13.04.2021 ТАСС Наука. Генетики локализовали причину нового психического расстройства https://nauka.tass.ru/nauka/11134105
18. 02.06.2021 Минобрнауки России. Российские ученые обнаружили новую мутацию, которая приводит к умственной отсталости https://www.minobrnauki.gov.ru/press-center/news/?ELEMENT_ID=34892