Zatsepin Laboratory

AboutTeamPublicationsFundingCollaborationThesis defencesCourses
Start date – September 2016

We run several projects devoted to RNA Biology and RNA Therapeutics in vitro and in vivo

1) RNA therapeutics based on modified antisense/siRNA/sgRNA with improved efficacy, biodistribution and stability in vivo.

We are working on the development of RNA-based therapeutics:

– novel antisense oligonucleotides that target RNA splicing to treat hereditary diseases in vitro and in vivo;

caged siRNA and hybrid nanoparticles to target liver diseases accompanied by inflammation;

– siRNA conjugates to validate targets in the liver;

chemically modified guide RNA for improved selectivity of genome editing

Joint projects with Prof. Gorin (CPQM, Skoltech)  on novel functional nanomaterials for RNA delivery in vitro and in vivo.

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2) Validation of RNA helicases and lncRNA as therapeutic targets in vitro and in vivo

Role of DDX3 helicase in the translation process and as a therapeutic target. Varied level of DDX3 allows us to reveal target mRNAs for DDX3 RNA helicase, hence, define and describe the exact role of DDX3 in translation in the mouse liver.

Role of LL35 lncRNA in the liver. We found that functional analog of the ncRNA DEANR1 in mouse – LL35 ncRNA is involved in the regulation of transcription. Transcriptome and proteome analysis revealed that LL35 can affect metabolic pathways in liver cells.

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Principal Investigator – Timofei Zatsepin  dsc1640_y

Team:

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Olga Sergeeva Tatiana Abakumova Nataliya Logvina
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Svetlana Dukova

 PhD Students:

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Denis Melnik Evgeniya Shcherbinina

Alumni:

Renata Ialchina, MS student in 2017-18; current: PhD student University of Copenhagen, Denmark Philipp Sergeev, MS student in 2018-19; current: PhD student in Institute for Molecular Medicine, Finland Mariia Nazarova, MS student in 2018-19; current: PhD student in The Research Institute of Molecular Pathology, Austria Svetlana Korinfskaya, MS student in 2017-18; current: PhD student in Cincinnati Children’s Hospital Medical Center, USA
Dr. Ilya Aparin, junior researcher in 2018-19 – current: postdoc in University of Strasbourg, France  Dominique LeboeufPhD student 2017-20; current: scientist in Beam Therapeutics, USA  Ilia Kopnin,  MS student in 2019-20; current: PhD student at KU Leuven, Belgium  Aleksandr Shikalov, MS student in 2019-20;
  • EEF2 depletion by RNAi in mouse liver leads to mTOR-independent translational upregulation of ribosomal genes. Gerashchenko M, Nesterchuk M, Smekalova E, Paulo J, Kowalski P, Gygi S, Rogorad B, Zatsepin T, Anderson D, Gladyshev V, Kotelianski V.  Sci. Rep., 10 (1), 15473 (2020).
  • DNA detection with dye-labeled oligonucleotides by surface enhanced Raman spectroscopy. Mendeleev Comm. Eremina O, Zatsepin T, Farzan V, Veselova I, Zvereva M, 30 (1), 18-21 (2020).

 

Current

Research grants/Industry funded research

Development of hybrid lipid nanoparticles containing Prussian blue for the suppression of reactive oxygen species and delivery of miRNA to the liver
Cancer cell-specific RNA interference in vivo
Novel chemical modifications in guide RNAs for improvement of genome editing by CRISPR-Cas9
Determination the role of RNA helicase DDX3 in the process of protein biosynthesis in vitro and in vivo
A novel strategy for pre-mRNA splicing correction by site-specific pre-miRNA recruitment
Nanoparticle-based drug delivery systems for intravital detection of reactive oxygen species

Completed

Research grants/Industry funded research

lncRNA LL35 as a regulator of Foxa 2 expression in vitro and in vivo - a probable target for diagnostics and therapeutics

Skoltech Biomedical Initiative

Magnetic nanoparticles and carbon nanotubes as enhancers for targeted RNA delivery in vivo

Next Generation Program: Skoltech – MIT Joint Projects

Regulation of Antitumor Response via Modulation of Ubr‐Ubiquitin Ligases In Vivo
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“Targeted RNA delivery in vivo for therapy by RNAi and genome editing” and “Regulation of Antitumor Response via Modulation of Ubr‐Ubiquitin Ligases In Vivo” Prof. Daniel Anderson, Massachusetts Institute of Technology

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“Novel RNA conjugates for targeted and functional RNA delivery” Prof. Vadim ShmanaiLaboratory of Bioconjugate Chemistry

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“Mechanisms of hepatocyte polarization in vivo” Prof. Marino ZerialZerial Lab

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​”Cancer cell – specific RNA interference in vivo” Prof. Dr. Andriy MokhirFriedrich-Alexander-Universität Erlangen-Nürnberg 

PhD 2020
MSc 2020
MSc 2019
MSc 2018
Instrumental Methods in Molecular Biology
RNA Biology