marlin biotech:next leap to treatgenetic diseases
DMD-AAV (preclinical)
SMA-AAV (preclinical)
Exon skipping for 6 and 7 exons of DMD gene (preclinical)
TergetHeart: delivery of morpholinos to heart (discovery)
Our technology
Antisense morpholino oligos
Marlin Biotech has built its own facility to produce GMP grade morpholino antisense molecules.
GENOME EDITING with CRISPR/Cas9
Marlin Biotech has successfully generated a custom model of DMD mouse with exons 8-34 deleted with CRISPR/Cas9 system.
AAV based gene delivery
We focus on AAV based gene delivery as AAVs look as the most promising vehicle to target human cells.
Exosome-based targeting
We develop a perspective method for delivery of genetic material and proteins to target tissue by exosomes. Exosomes possess higher capacity and reduced immunogenicity compared to AAV.
Our news
2018/08/21 - Start of the project "AAV-based delivery of utrophin shortened forms for DMD therapy", supported by Fund for Assistance to small innovative enterprises №359ГРНТИС5/42610 (www.fasie.ru)
2018/01/10 - Marlin Biotech launched new GNAO1 project.
2017/09/01 - iCELLis Nano bioreactor installation.
2017/07/01 - Start of the development of exosome-based targeting.
2017/06/15 - Marlin Biotech and Cure Duchenne held a conference for parents and physicians.
2016/07/05 - Marlin Biotech got a resident status of Skolkovo Innovation Center.
2016/01/18 - Marlin Biotech launched a service for animal and cell models creation with CRISPR/Cas9.
2015/12/05 - Marlin Biotech cryobank of primary cell cultures from patients with Duchenne muscular dystrophy got 100th cell line!
2015/11/04 - First 5 mice with deletion of exons 8-34 were born in Marlin Biotech trasgenic mice facility.
2015/07/08 - Marlin Biotech validated internal CRISPR/Cas9 protocol for genome edited mice model creation.
2015/02/16 - Marlin Biotech submitted documents to achieve Skolkovo Innovation Center resident status.
2014/09/15 - M29 was found to be non-toxic at 12 mg/kg dose.
2014/09/09 - Marlin Biotech created a cryobank of primary cell cultures from patients with Duchenne muscular dystrophy. More than 30 cell lines are collected to the date.
2014/07/13 - First toxicology experiments with M29 have started.
2014/05/23 - We have finished screening of antisense oligonucleotides for exon 6 and 7 skipping at DMD gene. M29 drug candidate was selected for following development.
PUBLICATIONS
1. Зотова Е.Д., Решетов Д.А., Жерновков В.Е., Димитриева Т.В., Дейкин А.В. Влодавец Д.В. «Анализ фенотипических проявлений делеций в гене дистрофина в контексте эффективности пропуска экзонов как метода терапии наследственных дистрофинопатий». Вестник РГМУ май-июнь 2016 (3). стр. 23-29. ISSN 2070-7320
2. Carlier P.G., Marty B., Scheidegger O., de Sousa P.L., Baudin P.Y., Snezchko E., Vlodavets D.V. «Роль количественной магнитно-резонансной томографии и спектроскопии скелетных мышц в оценке результатов клинических исследований» (Часть 1). «Нервно-мышечные болезни». 2016(4) Т6. с.10-20. ISSN 2222-8721.
3. Carlier P.G., Marty B., Scheidegger O., de Sousa P.L., Baudin P.Y., Snezchko E., D.V.Vlodavets, «Skeletal muscle quantitative nuclear magnetic resonance imaging and spectroscopy as an outcome measure for clinical trials». Journal of Neuromuscular Diseases, V3(1), 2016. p. 1-28. DOI 10.3233/JND-160145. ISSN 2214-3599 IOS Press
4. Влодавец Д.В., Казаков Д.О. «Диагностические возможности МРТ мышц при нервно-мышечных заболеваниях». Неврологический журнал «Медицина». 2014. стр. 4-12. ISSN 1560-9545
5. G. Tasca, M. Monforte, Jordi Díaz-Manera, G. Brisca, C. Semplicini, A. D'Amico, F. Fattori, A. Pichiecchio, A. Berardinelli, L. Maggi, E. Maccagnano, N. Løkken, C. Marini-Bettolo, F. Munell, A. Sanchez, N. Alshaikh, N.C. Voermans, J Dastgir, D. Vlodavets, J. Haberlová, G. Magnano, M.C. Walter, S. Quijano-Roy, R.-Y. Carlier, B.G.M. van Engelen, J. Vissing, V. Straub, C.G. Bönnemann, E. Mercuri, F. Muntoni, E. Pegoraro, E. Bertini, B. Udd, E. Ricci, C. Bruno. «MRI in sarcoglycanopathies: a large international cohort study». Journal of Neurology, Neurosurgery and Psychiatry. 2017 Sep 9. pii: jnnp-2017-316736. DOI: 10.1136/jnnp-2017-316736
6. Модификация метода анализа результатов редактирования генома м помощью системы CRISPR/Cas9 на предимплантационных эмбрионах мыши. Димитриева Т.В., Решетов Д.А., Жерновков В.Е., Влодавец Д.В., Зотова Е.Д., Ермолкевич Т.Г., Дейкин А.В. Вестник Российского государственного медицинского университета. 2016. № 3. С. 16-22.
7. Maxim S. Kupryushkin, Mikhail D. Nekrasov, Dmitry A. Stetsenko, and Dmitrii V. Pyshnyi.
Efficient Functionalization of Oligonucleotides by New Achiral Nonnucleosidic Monomers
Organic Letters 2014 16 (11), 2842-2845 DOI: 10.1021/ol500668n
8. A.A. Lomzov, M.S. Kupryushkin, A.V. Shernyukov, M.D. Nekrasov, I.S. Dovydenko, D.A. Stetsenko, D.V. Pyshnyi
Diastereomers of a mono-substituted phosphoryl guanidine trideoxyribonucleotide: Isolation and properties
Biochemical and Biophysical Research Communications, doi:10.1016/j.bbrc.2019.04.024, IF=2.559
9. Hannah K. Robinson, Alexey V. Deykin, Evgeny V. Bronovitsky, Ruslan K. Ovchinnikov, Alexey A. Ustyugov, Tatyana A. Shelkovnikova, Michail S. Kukharsky, Tatyana G. Ermolkevich, Igor L. Goldman, Elena R. Sadchikova, Elena A. Kovrazhkina, Sergey O. Bachurin, Vladimir L. Buchman & Natalia N. Ninkina (2015)Early lethality and neuronal proteinopathy in mice expressing cytoplasm-targeted FUS that lacks the RNA recognition motif, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 16:5-6, 402-409, DOI: 10.3109/21678421.2015.1040994
11. Yaroslav Gursky, Robert Bibilashvili, Mikchail Minashkin, Alex Krasnov, Alex Deikin, Tatyana Ermolkevich, Andrey Popov, Lilia Verbovaya, Nicolai Rutkevich, Alexsander Shevelev, Sofia Georgieva, Sergey V. Razin, Igor Goldman, Elena Sadchikova. Expression of full-length human pro-urokinase in mammary glands of transgenic mice. Transgenic Res (2009) 18: 747. https://doi.org/10.1007/s11248-009-9269-9
12. Yu. Yu. Silaeva, A. A. Kalinina, M. S. Vagida, L. M. Khromykh, A. V. Deikin, T. G. Ermolkevich, E. R. Sadchikova, I. L. Goldman, D. B. Kazansky. Decrease in pool of T lymphocytes with surface phenotypes of effector and central memory cells under Influence of TCR transgenic β-chain expression. Biochemistry Moscow (2013) 78: 549. https://doi.org/10.1134/S0006297913050143
13. E. S. Zvezdova, Yu. Yu. Silaeva, M. S. Vagida, E. V. Maryukhnich, A. V. Deikin, T. G. Ermolkevich, S. G. Kadulin, E. R. Sadchikova, I. L. Goldman, D. B. Kazansky. Generation of transgenic animals expressing the α and β chains of the autoreactive T-cell receptor
Mol Biol (2010) 44: 277. https://doi.org/10.1134/S0026893310020135
14. I.L. Goldman,ab S.G. Georgieva,ac Ya.G. Gurskiy,a A.N. Krasnov,a A.V. Deykin,ab A.N. Popov,a T.G. Ermolkevich,ab A.I. Budzevich,d A.D. Chernousov,a E.R. Sadchikovaac Production of human lactoferrin in animal milkBiochemistry and Cell Biology, 2012, 90(3): 513-519, https://doi.org/10.1139/o11-0888.
15. R. V. Zvartsev, D. S. Korshunova, E. A. Gorshkova, M. A. Nosenko, K. V. Korneev, O. G. Maksimenko, I. V. Korobko, D. V. Kuprash, M. S. Drutskaya, S. A. Nedospasov, A. V. Deikin. Neonatal Lethality and Inflammatory Phenotype of the New Transgenic Mice with Overexpression of Human Interleukin-6 in Myeloid Cells
Dokl Biochem Biophys (2018) 483: 344. https://doi.org/10.1134/S1607672918060157
16. Victor Yu. Glanz, Alexander N. Orekhov*, Alexey V. Deykin. Human Disease Modelling Techniques: Current Progress. Current Molecular Medicine. Volume 18 , Issue 10 , 2018
conference reports
1. Reshetov D.A., Artemieva S.B., Litvinova E.B., Shulyakova I.V., Shidlovskaya O.A.,Kazakov D.O., Belousova E.D., Vlodavets D.V. «Russian experience of DMD Genetic Database». Neuromuscular Disorders. 2016: V26(Suppl.2). ISSN 0960-8966 http://dx.doi.org/10.1016/j.nmd.2016.06.045
2. D.Vlodavets, M.Komarova, D.Reshetov. «A case report of a 10 year old boy with combination of DMD and Dawn Syndrome». Journal of Neuromuscular Diseases, V3 S1. p. 143-144. ISSN 2214-3599
3. T.Dimitrieva, A.Deikin, D.Reshetov, D.Vlodavets, E.Zotova. «Novel mouse model of Duchenne muscular dystrophy with deletion of exons 8-34». Journal of Neuromuscular Diseases, V3 S1. p. 142. ISSN 2214-3599
4. Reshetov D.A., Vlodavets D.V. «Open access cryobank of primary cell cultures from Duchenne muscular dystrophy patients». «Acta Myologica». Vol. XXXIV – May 2015. p. 33. ISSN 1128-2460
5. New insight into exon-skipping approach for Duchenne muscular dystrophy treatment. Tatiana V. Egorova and Alexei V. Deikin, J Stem Cell Res Ther 2018, Volume 8. DOI: 10.4172/2157-7633-C1-033
6. Expression of dystrophin isoforms in new Duchenne muscular dystrophy mice model. Tatiana Egorova , Dmitry Vlodavets , Denis Reshetov , Evgenia Zotova , Anna Polikarpova , Svetlana Vassilieva , Alexei Deikin. Journal of Neuromuscular Diseases, vol. 5, no. s1, pp. S1-S408, 2018
7. Exons 6 and 7 skipping test on new murine model of Duchenne muscular dystrophy. T. T. Egorova, D. Reshetov, A. Polikarpova, S. Vassilieva, D. Vlodavets, A. Deikin. October 2018. Neuromuscular disorders. Vol.28. S.94.
8. Microutrophin delivery shows phenotype improvement in mdx mice. T. Egorova, D. Vlodavets, A. Starikova, A. Polikarpova, A. Shmidt, N. Trushkin, E. Luchkina, S. Vassilieva, E. Usachev, A. Deikin. October 2018. Neuromuscular disorders. Vol.28. S.93.
Russian conference
2020.12.11 - RUSSIAN MEDICAL AND PATIENT CONFERENCE "Standards and achievements in the field of diagnosis, rehabilitation, management and treatment of Duchenne myodystrophy"
Resolution of the conference MDD_16.12.2020 .docx
2017.06.15 - CONFERENCE "Duchenne muscular dystrophy" WITH MARLIN BIOTECH AND CURE DUCHENNE
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