Genome Engineering Lab

The Genome Engineering Lab, or Gel, has several key projects, all of them involving genome editing mediated by the CRISPR/Cas technology. Discovered just a few years ago, CRISPR/Cas has emerged as one of the hottest scientific trends. This technology is speeding up the approach of a futuristic era when genome modifications will permeate human existence.

At Gel, we seek answers to the how questions:
• How do we edit the genome?
• How do we cure incurable diseases?
• How do we improve our lives? And so on …

Gel focuses on discovering new effectors — molecular scissors, which are a key component of the CRISPR/Cas technology. The reason is that for complex genome editing, we need instruments that are way more sophisticated and specific than what we currently have.

We are trying to implement genome editing technologies for developing two kinds of therapies:
• Firstly, we are working on engineered T cells for cancer treatment, because we believe that the immune system is capable of controlling most oncological states. It just needs a little help.
• Secondly, we are developing a technology for generating hematopoietic stem cells to address the bone marrow transplantation problem.

The global demand on bone marrow transplantations is on the order of 5 million procedures annually. However, fewer than 50,000 transplantations per year are made. Unfortunately, it is not always possible to find a compatible donor, but everyone is fully genetically compatible with themselves. So if it becomes possible to make hematopoietic stem cells from a patient’s own tissue, the donation and compatibility issue will be resolved.

As new effectors are discovered, another part of the team takes over to test and implement them for endowing plants and animals with the necessary properties. For instance, this enables the creation of birds resistant to influenza. These studies are in close contact with the current problems of the biotech, agricultural, and food industries. In the future, they will allow companies to avoid the enormous losses that arise due to diseases caused by viruses.

By extension, genetic modification is a way to address the risk of natural selection producing mutations that could give the virus an opportunity to overcome the interspecies barrier, infecting humans and potentially leading to a pandemic. Given the present-day scale of populations, this is more likely than we would wish.

2018

BMC Biotechnology

Efficient generation of Rosa26 knock-in mice using CRISPR/Cas9 in C57BL/6 zygotes

Van Trung Chu, Timm Weber, Robin Graf, Thomas Sommermann, Kerstin Petsch, Ulrike Sack, Pavel Volchkov, Klaus Rajewsky, Ralf Kühn

Moscow Institute of Physics and Technology

2017

Oncogenesis

Spatial distribution of disease-associated variants in three-dimensional structures of protein complexes

Gress, A., Ramensky, V., and Kalinina, O.V.

Moscow Institute of Physics and Technology

Neuron

Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome

Huang, A.Y., Yu, D., Davis, L.K., Sul, J.H., Tsetsos, F., Ramensky, V., Zelaya, I., Ramos, E.M., Osiecki, L., Chen, J.A., et al.

Moscow Institute of Physics and Technology

Nature Genetics

Genetic variation and gene expression across multiple tissues and developmental stages in a non-human primate

Jasinska A., Zelaya I., Service S., Peterson, C., et al.

Moscow Institute of Physics and Technology

Nature Genetics

Ancient hybridization and strong adaptation to viruses across African vervet monkey populations

Svardal, H., Jasinska A.J., Apetrei, C., Coppola G., et al.

Moscow Institute of Physics and Technology

Neuron

De Novo Coding Variants Are Strongly Associated with Tourette Disorder

Willsey, A.J., Fernandez, T.V., Yu, D., King, R.A., Dietrich, A., Xing, J., Sanders, S.J., Mandell, J.D., Huang, A.Y., Richer, P., et al.

Moscow Institute of Physics and Technology

2016

Nucleic Acids Research

StructMAn: annotation of single-nucleotide polymorphisms in the structural context

Gress, A., Ramensky, V., Büch, J., Keller, A., and Kalinina, O.V.

Moscow Institute of Physics and Technology

Clinical Cancer Research

A novel HSP90 inhibitor-drug conjugate to SN38 is highly effective in small cell lung cancer (SCLC)

Gaponova AV, Nikonova A, Deneka AY, Kopp MC, Kudinov AE, Skobeleva N, Khazak V, Shin Ogawa L ,Cai KQ,Duncan KE, Duncan JS,Egleston BL, Proia DA, Boumber Y, Golemis EA

Moscow Institute of Physics and Technology

2015

Proceedings of the National Academy of Sciences

Toll-like receptor signaling involvement in regulation of type 1 diabetes by microbiota

Michael Burrows, Pavel Volchkov, Koichi Kobayashi and Alexander Chervonsky

Moscow Institute of Physics and Technology

Annals of Medicine

The safety of human pluripotent stem cells in clinical treatment

Oscar Simonson, Anna Domogatskaya, Pavel Volchkov and Sergey Rodin

Moscow Institute of Physics and Technology

BMC Biology

Sequencing strategies and characterization of 721 vervet monkey genomes for future genetic analyses of medically relevant traits

Huang, Y.S., Ramensky, V., Service, S.K., Jasinska, A.J., Jung, Y., Choi, O.-W., Cantor, R.M., Juretic, N., Wasserscheid, J., Kaplan, J.R., et al.

Moscow Institute of Physics and Technology

Genome Research

The genome of the vervet (Chlorocebus aethiops sabaeus)

Warren, W.C., Jasinska, A.J., García-Pérez, R., Svardal, H., Tomlinson, C., Rocchi, M., Archidiacono, N., Capozzi, O., Minx, P., Montague, M.J., et al.

Moscow Institute of Physics and Technology

Gene

Preclinical and clinical studies of the NEDD9 scaffold protein in cancer and other diseases

Shagisultanova E, Gaponova AV, Gabbasov R, Nicolas E, Golemis EA

Moscow Institute of Physics and Technology

Polar Biology

A new species of Cyanea jellyfish sympatric to C. capillata in the White Sea

Kolbasova Glafira D., Zalevsky Arthur O., Gafurov Azamat R., Gusev Philipp O., Ezhova Margarita A., Zheludkevich Anna A., Konovalova Olga P., Kosobokova Ksenia N., Kotlov Nikita, Lanina Natalia O., Lapashina Anna S., Medvedev Dmitry O., Nosikova Katerina S., Nuzhdina Ekaterina O., Bazykin Georgii A., Tatyana Neretina

Moscow Institute of Physics and Technology

2014

Cell

Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors

Riddell, Roi Gazit, Brian S Garrison, Guoji Guo, Assieh Saadatpour, Pankaj K Mandal, Wataru Ebina, Guo-Cheng Yuan, Pavel Volchkov, Stuart H Orkin, Derrick J Rossi

Moscow Institute of Physics and Technology

PLoS Genetics

Re-sequencing Expands Our Understanding of the Phenotypic Impact of Variants at GWAS Loci

Service, S.K., Teslovich, T.M., Fuchsberger, C., Ramensky, V., Yajnik, P., Koboldt, D.C., Larson, D.E., Zhang, Q., Lin, L., Welch, R., et al.

Moscow Institute of Physics and Technology

IUBMB Life

CAS proteins in health and disease: an update

Nikonova AS, Gaponova AV, Kudinov AE, Golemis EA

Moscow Institute of Physics and Technology

2013

Immunity

Gender bias in autoimmunity is influenced by microbiota

Yurkovetskiy L, Burrows M, Khan AA, Graham L, Volchkov P, Becker L, Antonopoulos D, Umesaki Y, Chervonsky AV

Moscow Institute of Physics and Technology

2010

Journal of Experimental Medicine

A critical role for Treg cell-mediated control of inflammation in the absence of commensal microbiota

Takatoshi Chinen, Pavel Volchkov, Alexander Chervonsky, Alexander Rudensky

Moscow Institute of Physics and Technology

Nature Methods

A method and server for predicting damaging missense mutations

Adzhubei, I.A., Schmidt, S., Peshkin, L., Ramensky, V.E., Gerasimova, A., Bork, P., Kondrashov, A.S., and Sunyaev, S.R.

Moscow Institute of Physics and Technology

Current Opinion in Structural Biology

Human allelic variation: perspective from protein function, structure, and evolution

Jordan, D.M., Ramensky, V.E., and Sunyaev, S.R.

Moscow Institute of Physics and Technology

Biology Direct

Asymmetric and non-uniform evolution of recently duplicated human genes

Panchin, A.Y., Gelfand, M.S., Ramensky, V.E., and Artamonova, I.I.

Moscow Institute of Physics and Technology

2009

Encyclopedia of Life Sciences

Positive Selection and Alternative Splicing in Humans

Gelfand, M.S., and Ramensky, V.E.

Moscow Institute of Physics and Technology

Journal of Bacteriology

Maturation of the translation inhibitor microcin C

Metlitskaya, A., Kazakov, T., Vondenhoff, G.H., Novikova, M., Shashkov, A., Zatsepin, T., Semenova, E., Zaitseva, N., Ramensky, V., Van Aerschot, A., et al.

Moscow Institute of Physics and Technology

BMC Medical Genomics

Network analysis of human glaucomatous optic nerve head astrocytes

Nikolskaya T, Nikolsky Y, Serebryiskaya T, Zvereva S, Sviridov E, Dezso Z, Rahkmatulin E, Brennan RJ, Yankovsky N, Bhattacharya SK, Agapova O, Hernandez MR, Shestopalov VI

Moscow Institute of Physics and Technology

Methods in Molecular Biology

Manual annotation of protein interactions

Bureeva S, Zvereva S, Romanov V, Serebryiskaya T.

Moscow Institute of Physics and Technology

2008

Nature

Innate immunity and intestinal microbiota in the development of Type 1 diabetes

Wen L, Ley R. E., Volchkov P. Y, Stranges P. B., Avanesyan L., Stonebraker A. C., Hu C.,Wong F. S., Szot G. L., Bluestone J. A., Gordon J. I., Chervonsky A. V.

Moscow Institute of Physics and Technology

Cell Cycle

CD30 is a marker of undifferentiated human embryonic stem cells rather than a biomarker of transformed hESCs

Lagarkova M. A., Volchkov P., Philonenko E. S., Pfannkuche K,. Prokhorovich M. A., Zabotina T., Hescheler J., Kiselev S. L.

Moscow Institute of Physics and Technology

Cell Cycle

Efficient differentiation of hESCs into endothelial cells in vitro is secured by epigenetic changes

Lagarkova M. A., Volchkov P., Philonenko E. S., Kiselev S. L.

Moscow Institute of Physics and Technology

American Journal of Human Genetics

Positive Selection in Alternatively Spliced Exons of Human Genes

Ramensky, V.E., Nurtdinov, R.N., Neverov, A.D., Mironov, A.A., and Gelfand, M.S.

Moscow Institute of Physics and Technology

2007

Cellular Transplantology and Tissue Engineering

Negative control of genes during differentiation of embryonic stem cells into endothelial cells

Volchkov P. Y, Lagarkova M. A., Prokhorovich M. A., Kiselev S. L.

Moscow Institute of Physics and Technology

Proteins

A novel approach to local similarity of protein binding sites substantially improves computational drug design results

Ramensky, V., Sobol, A., Zaitseva, N., Rubinov, A., and Zosimov, V.

Moscow Institute of Physics and Technology

2006

Cell Cycle

Diverse epigenetic profile of novel human embryonic stem cell lines

Lagarkova M. A., Volchkov P. Y., Lyakisheva A. V., Philonenko E. S., Kiselev S. L.

Moscow Institute of Physics and Technology

Molecular Medicine

Molecular and cellular biology of human embryonic stem cells

Kiselev S. L., Volchkov P. Y, Prokhorovich M. A., Mufazalov I. A., Lyakisheva A. V., Lagarkova M. A.

Moscow Institute of Physics and Technology

Biofizika

EDAS, databases of alternatively spliced human genes

Nurtdinov, R.N., Neverov, A.D., Mal’ko, D.B., Kosmodem’ianskiĭ, I.A., Ermakova, E.O., Ramenskiĭ, V.E., Mironov, A.A., and Gel’fand, M.S.

Moscow Institute of Physics and Technology

2005

Nucleic Acids Research

A retrocopy of a gene can functionally displace the source gene in evolution

Krasnov, A.N., Kurshakova, M.M., Ramensky, V.E., Mardanov, P.V., Nabirochkina, E.N., and Georgieva, S.G.

Moscow Institute of Physics and Technology

2004

Doklady Biochemistry and Biophysics

Reciprocal dependence between pectinmethylesterase gene expression and tobamovirus reproduction effectiveness in Nicotiana benthamiana

Dorokhov YL, Skurat EV, Frolova OY, Gasanova TV, Smirnov AA, Zvereva SD, Ivanov PA, Ravin NV, Zamchuk LI, Atabekov IG

Moscow Institute of Physics and Technology

Journal of General Virology

Evidence for contribution of an internal ribosome entry site to intercellular transport of a tobamovirus

Zvereva SD, Ivanov PA, Skulachev MV, Klyushin AG, Dorokhov YL, Atabekov JG

Moscow Institute of Physics and Technology

2003

Nucleic Acids Research

The human genome contains many types of chimeric retrogenes generated through in vivo RNA recombination

Buzdin A., Gogvadze E., Kovalskaya E., Volchkov P., Ustyugova S., Illarionova A., Fushan A., Vinogradova T., Sverdlov E.

Moscow Institute of Physics and Technology

Human Molecular Genetics

Impact of selection, mutation rate and genetic drift on human genetic variation

Sunyaev, S., Kondrashov, F.A., Bork, P., and Ramensky, V.

Moscow Institute of Physics and Technology

Russian Journal of Plant Physiology

Transgenic Brassica campestris Plants Expressing the gfp Gene

S.I. Malyshenko, L.G. Tyul'kina, S.D. Zvereva, G.N. Raldugina

Moscow Institute of Physics and Technology

Plant Physiology and Biochemistry

Agrobacterium–mediated transformation and stable expression of the green fluorescent protein in Brassica rapaPlant Physiology and Biochemistry

Tony Wahlroos, Petri Susi, Lidia Tylkina, Svetlana Malyshenko, Svetlana Zvereva, Timo Korpela

Moscow Institute of Physics and Technology

2002

Nucleic Acids Research

Human non-synonymous SNPs: server and survey

Ramensky, V., Bork, P., and Sunyaev, S.

Moscow Institute of Physics and Technology

Proceedings of the National Academy of Sciences

Polypurine (A)-rich sequences promote cross-kingdom conservation of internal ribosome entry

Dorokhov YL, Skulachev MV, Ivanov PA, Zvereva SD, Tjulkina LG, Merits A, Gleba YY, Hohn T, Atabekov JG

Moscow Institute of Physics and Technology

2001

Computational Biology

Bayesian Approach to DNA Segmentation into Regions with Different Average Nucleotide Composition

Makeev, V., Ramensky, V., Gelfand, M., Roytberg, M., and Tumanyan, V.

Moscow Institute of Physics and Technology

Sar And Qsar In Environmental Research

Molecular modelling of disease-causing single-nucleotide polymorphisms in collagen

Milchevsky, J.V., Ramensky, V.E., Esipova, N.G., Tumanyan, V.G., and Zorov, B.S.

Moscow Institute of Physics and Technology

Bioinformatics

Segmentation of long genomic sequences into domains with homogeneous composition with BASIO software

Ramensky, V.E., Makeev, V.J., Roytberg, M.A., and Tumanyan, V.G.

Moscow Institute of Physics and Technology

Human Molecular Genetics

Prediction of deleterious human alleles

Sunyaev, S., Ramensky, V., Koch, I., Lathe, W., Kondrashov, A.S., and Bork, P.

Moscow Institute of Physics and Technology

2000

Biofizika

How do point amino acid substitutions affect the protein structure?

Ramenskiĭ, V.E., Vlasov, P.K., Siuniaev, S.R., and Tumanian, V.G.

Moscow Institute of Physics and Technology

Russian Journal of Plant Physiology

Reporter genes for plant genetic engineering: Characteristics and detection

S. Zvereva, G.A. Romanov

Moscow Institute of Physics and Technology

Journal of Computational Biology

DNA segmentation through the Bayesian approach

Ramensky, V.E., Makeev VJu, Roytberg, M.A., and Tumanyan, V.G.

Moscow Institute of Physics and Technology

Trends in Genetics

Towards a structural basis of human non-synonymous single nucleotide polymorphisms

Sunyaev, S., Ramensky, V., and Bork, P.

Moscow Institute of Physics and Technology

Trends in Genetics

SNP frequencies in human genes an excess of rare alleles and differing modes of selection

Sunyaev, S.R., Lathe, W.C., Ramensky, V.E., and Bork, P.

Moscow Institute of Physics and Technology