Laboratory of RNA Chemistry

Aliya G. Venyaminova,
Ph.D.
The Russia State Prize in Science and Technique (1999)
Prize of International Publishing Company “Nauka/Interperiodika” (2010)

Phone: +7(383) 363-51-29; Email

• Development of different approaches for synthesis of oligoribonucleotides, their analogs and derivatives as artificial inhibitors of gene expression, biosensors and tools for studying of NA-NA and NA-proteins interactions

- Small interfering RNA (siRNA) and their modified analogs with improved physical, chemical, biological and pharmacological properties
- Modified RNA aptamers stable in biological systems as promising tools for diagnostics and therapy
- Antisense and antigene reagents and probes based on 2’-O-modified oligoribonucleotides
- Technologies of a mid-scale automatiс synthesis of oligoribonucleotides, their analogs and conjugates

• Design of multifunctional constructions based on oligonucleotides and synthetic organic and inorganic nanocarriers as biosensor nanoplatforms and perspective tools of theranoctics

• Solid phase synthesis methods of oligoribonucleotides and their 2’-O-modified analogs as basic structures for design of gene targeted biologically active compounds were developed.

Synthetic protocols for oligoribonucleotides and their analogs using automated synthesizer ASM 800 and plate synthesizer ASM 1000 and ASM 2000 (BIOSSET, Russia) were developed. These results provide support for scientific research in Laboratory of RNA chemistry and other laboratories of ICBFM SB RAS.

• A broad spectrum of new conjugates of oligoribonucleotides and their 2’-O-methyl-analogs bearing alkylating, photocrosslinking, triplex formation, intercalating, hydrophobic, fluorescent groups were created for targeting of biopolymers. A part of these studies was honoured by the Russian State Prize (1999). A new approach to the functionalization of heterocyclic bases in oligoribonucleotides was developed. This allows to design various conjugates to study RNA-NA and RNA-protein interactions. [Repkova M.N. et al., Bioorgan. Chemistry (Russia). 1999. 25, 699; Russ. Chem. Bull., Int. Ed. 2002. 51, 1194; Nucl. Nucl. Nucleic Acids. 2003. 22, 1509; 2004. 23, 969].
• The series of new photoactivatable analogs of mRNA were synthesized and successfully used as tools for research of mRNA binding center in human ribosomes (please see the page of Laboratory of structure and function of ribosomes ICBFM SB RAS). New triplex formation conjugates based on oligo(2’-O-methylribonucleotides) carrying “inverted” thymidine at the 3’-end and minor groove ligands and triplex specific intercalator at the 5’-end were designed. The ability of these conjugates to inhibit transcription in vitro was demonstrated. [Novopashina D.S. et al., Chem. Biodiv. 2005. 2, 936; Halby L. et al., J. Biomol. Struct. Dyn. 2007. 25, 61; Novopashina D.S. et al., Bioorgan. Chemistry (Russia). 2013. 39, 159].
• 5’-, 3’- and 2’- mono- and bis-pyrene conjugates of oligo(2’-O-methylribonucleotides) and multipyrene tandem constructions were synthesized for the first time. These constructions are perspective fluorescent probes for investigation of oligonucleotide hybridization with NA, detection of different type mutations in the DNA and detection of RNA in solution. [Novopashina D.S. et al., Nucl. Nucl. Nucleic Acids. 2005. 24, 729; 2007. 26, 821; Krasheninina O.A., Bioorgan. Chemistry (Russia). 2011. 37, 244; Novopashina D.S. et al., Vestnik NSU. Series: Biology and Clinical Medicine. 2011. 9, 15].
• A new approach to design of biologically stable binary NA enzymes based on hammerhead ribozyme and 10-23 DNAzyme was proposed. Binary constructs were shown to cleave effectively both short RNA substrates and extended native folded RNAs (through the example of MDR1 mRNA and IGF-IR mRNA). [Vorobjeva M. et al., Oligonucleotides. 2006. 16, 239; Vorobjeva M.A. et al., Russ. Chem. Rev. 2011. 80, 127]. Nuclease-resistant 2’-O-methylated DNAzymes efficiently inhibit the IGF-I gene function in living cells. [Fokina A.A. et al., Biochemistry. 2012. 51, 2181].
• New approaches for synthesis of modified siRNA and their conjugates with improved physico-chemical and biological characteristics were developed. [Volkov A.A. et al., Oligonucleotides. 2009. 19, 191; Kruglova N.S. et al., Molecular Biology (Russia). 2010. 44, 254; Petrova (Kruglova) N.S. et al., Oligonucleotides. 2010. 20, 297; Nucleic Asids Res. 2012. 40, 2330; Durfort T. et al., PLoS ONE. 2012. 7, e29213].
• Approaches to the synthesis of multifunctional carbon nanotubes have been developed. Such multifunctional carbon nanotubes could be used as a platform for design of biocompatible transporters of nucleic acids, biosensors and theranostics tools. [Apartsin E.K. et al., Vestnik NSU. Series: Biology and Clinical Medicine. 2012. 10, 181; Apartsin E.K. et al., Nanotechnol. Russ. 2012. 7, 99; Novopashina D.S. et al. Ukr. J. Phys. 2012, 57, 718]. A model of electrochemical biosensor for detection of specific NA sequences was constructed (in collaboration with Institute of inorganic chemistry SB RAS). [Fedorovskaya E.O. et al., Patent request RF N.2011143078, 2011].
• We obtained for the first time 2'-fluoro-modified RNA aptamers against human insulin-like growth factor I (IGF IR) on a cell surface [Davydova A.S. et al., Acta Naturae. 2011. 3, 12; Davydova A. et al., Coll. Symp. Ser. Chemistry of Nucleic Acid Components. 2011, 12, 416; Davydova A.S. et al., Mol. Biol. (Rus.). 2013. 47, 904] and 2'-fluoro-modified RNA aptamers for specific recognizing of pathogenic autoantibodies associated with multiple sclerosis [Tivanova A.S. et al., Coll. Symp. Ser. Chemistry of Nucleic Acid Components. 2011. 12, 419; Tivanova A.S. et al., FEBS Journal. 2011. 278, 164], and investigated their properties. New conjugate of the aptamer against MS-related autoantibodies with Са2+-regulated photoprotein obelin was obtained and the proof-of-principle for bioluminescent detection of target antibodies using this conjugate was demonstrated. [Vorobjeva M.A. et al., Anal. Chem. 2014. 86, 2590].

1. Gvozdeva O.V., Dovydenko I.S., Venyaminova A.G., Zenkova M.A., Vlassov V.V., Chernolovskaya E.L. 42- and 63-bp anti-MDR1-siRNAs bearing 2'-OMe modifications in nuclease-sensitive sites induce specific and potent gene silencing. FEBS Lett. 2014. 588(6), 1037-1043.
2. Hégarat N., Novopashina D., Fokina A.A., Boutorine A.S., Venyaminova A.G., Praseuth D., François J.C. Monitoring DNA triplex formation using multicolor fluorescence and application to insulin-like growth factor I promoter downregulation. FEBS J. 2014. 281(5), 1417-1431.
3. Apartsin E.K., Buyanova M.Y., Novopashina D.S., Ryabchikova E.I., Filatov A.V., Zenkova M.A., Venyaminova A.G. Novel multifunctional hybrids of single-walled carbon nanotubes with nucleic acids: synthesis and interactions with living cells. ACS Appl Mater Interfaces. 2014. 6(3), 1454-1461.
4. Vorobjeva M.A., Krasitskaya V.V., Fokina A.A., Timoshenko V.V., Nevinsky G.A., Venyaminova A.G., Frank L.A. RNA Aptamer against Autoantibodies Associated with Multiple Sclerosis and Bioluminescent Detection Probe on Its Basis. Anal Chem. 2014. 86(5), 2590-2594.
5. Kholodar S.A., Novopashina D.S., Meshchaninova M.I., Venyaminova A.G. Multipyrene tandem probes for point mutations detection in DNA. J. of Nucleic Acids. 2013. 1-12.
6. Butorin A., Novopashina D.S., Krasheninina O.A., Nozeret K., Venyaminova A.G. Fluorescent Probes for Nucleic Acid Visualization in Fixed and Live Cells. Molecules. 2013. 18(12), 15357-15397.
7. Davydova A.S., Vorobjeva M.A., Zenkova M.A., Silnikov V.N., François J.C., Venyaminova A.G. New cellular RNA elimination method for cell-based SELEX of modified RNA aptamers. Mol. Biol. (Rus.). 2013. 47 (6), 904-906.
8. Novopashin S.A., Serebryakova M.A., Sokolov R.E., Zaikovskii A.V., Okotrub A.V., Novopashina D. S. Heat conductivity of a nanoliquid based on water and chemically modified single walled carbon nanotubes . Nanotechnol. Russ., 2013, 8(1–2), 64–68.
9. Novopashina D. S., Sinyakov A. N., Ryabinin V. A., Perrouault L., Giovannangeli C., Venyaminova A. G., Boutorine A. S. Oligo(2′-O-methylribonucleotides) and their derivatives: IV. Conjugates of oligo(2′-O-methylribonucleotides) with minor groove binders and intercalators: Synthesis, properties, and application. Russ. J. Bioorg. Chem. 39 (2), 138-152.
10. Fokina A.A., Meschaninova M.I., Durfort T., Venyaminova A.G., François J.-C. Targeting Insulin-like growth factor I with 10-23 DNAzymes: 2’-O-methyl modifications in catalytic core enhance mRNA cleavage. Biochemistry. 2012. 51, 2181-2191.
11. Durfort T., Tkach M., Meschaninova M.I., Rivas M.A., Elizalde P.V., Venyaminova A.G., Schillaci R., François J.-C. Small interfering RNA targeted to IGF-IR delays tumor growth and induces proinflammatory cytokines in a mouse breast cancer model. PLoS One. 2012. 7(1), e29213.
12. Petrova N.S., Chernikov I.V., Meschaninova M.I., Dovydenko I.S., Venyaminova A.G., Zenkova M.A., Vlassov V.V., Chernolovskaya E.L. Carrier-free cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group. Nucleic Acids Res. 2012. 40(5), 2330-2344.
13. Sharifulin D.E., Khairulina Y.S., Ivanov A.V., Meshchaninova M.I., Venyaminova A.G., Graifer D.M., Karpova G.G. A central fragment of ribosomal protein S26 containing the eukaryote-specific motif YxxPKxYxK is a key component of the ribosomal binding site of mRNA region 5’ of the E site codon. Nucleic Acids Res. 2012. 40(7), 3056-3065.
14. Kabilova T.O., Meshchaninova M.I., Venyaminova A.G., Nikolin V.P., Zenkova M.A., Vlassov V.V., Chernolovskaya E.L. Short Double-Stranded RNA with Immunostimulatory Activity: Sequence Dependence. Nucleic Acid Ther. 2012. 22(3), 196-204.
15. Novopashina D.S., Apartsin E.K., Venyaminova A.G. Fluorescently labeled bionanotransporters of nucleic acids based on carbon nanotubes. Ukr. J. Phys. 2012. 57(7), 718-722.
16. Apartsin E.K., Novopashina D.S., Nastaushev Y.V., Venyaminova A.G. Fluorescently labeled single-walled carbon nanotubes and their hybrids with oligonucleotides. Nanotechnologies in Russia. 2012. 7(3-4), 99-109.
17. Krasheninina O.A., Novopashina D.S., and Venyaminova A.G. Oligo(2'-O-methylribonucleotides) containing insertions of 2'-bispyrenylmethylphosphorodiamidate nucleoside derivatives as prospective fluorescent probes for RNA detection. Russ. J. of Bioorg. Chem. 2011. 37(2), 244-248.
18. Vorobjeva M.A, Davydova A.S. and Venyaminova A.G. Artificial hammerhead ribozymes: engineering and applications. Russ. Chem. Rev. 2011. 80(2), 127-143.
19. Bulygin K.N., Khairulina Y.S., Kolosov P.M., Ven'yaminova A.G., Graifer D.M., Vorobjev Y.N., Frolova L.Y., Karpova G.G. Adenine and guanine recognition of stop codon is mediated by different N domain conformations of translation termination factor eRF1. Nucleic Acids Res. 2011. 39(16), 7134-7146.
20. Davydova A.S., Vorobjeva M.A., Venyaminova A.G. Escort-aptamers: new tools for the targeted delivery of therapeutics into cells. Acta Naturae. 2011. 3(4), 12-29.

1. Fedorovskaja E.O., Apartsin E.K., Novopashina D.S., Bulusheva L.G., Ven'jaminova A.G., Okotrub A.V. Detection method of specific sequences of nucleic acids (versions), and device for its realization. Patent RF N.2509157, 2014.

RFBR (Grants of the Russian Foundation for Basic Research)

• N.12-04-91053 Project RFBR-CNRS (France) (PICS 2012) “Development of fluorescent sequence-specific probes for studies of the localization, dynamics and biological role of nucleic acids in living cells” (2012-2014)
• N.14-04-01611 “Aptasensors based on 2’-modified RNA aptamers for the detection of autoantibodies associated with multiple sclerosis” (2014-2016)
• N.14-04-31961_mol_a “Multifunctional hybrids of nucleic acid constructions with carbon nanotubes for the delivery of therapeutic nucleic acids into cells” (2014-2015)
• N.14-04-31510_mol_a “RNA aptasensors for IGF-IR receptor detection on the cell surface” (2014-2015)

Interdisciplinary integration project of the Presidium of SB RAS

• N.85 “Chemically modified small interfering RNAs for overcoming of tumor multidrug-resistance” (2012-2014)

International projects
7th Framework Program (FP7)

• NANOGENE project (PIRSES–GA-2012-316730) «EU-Belarus-Russia Network in Nanomaterials-Driven Anti-Cancer Therapy» (2013-2016)

Individual grants for young scientists

• Project of the program «A participant of youth scientific innovative contest 2012»
• «Highly specific diagnostics of malignant diseases by means of aptasensors», 2012-2014 (Davydova A.S.)
• «Aptasensors based on 2'-modified RNA aptamers for detection of autoantibodies associated with multiple sclerosis», 2013-2015 (Timoshenko V.V.)

Russian President's scholarship for young scientists and post-graduate students

• SP-6266.2013.4 «The hybrids of NA constructs with carbon nanotubes for the development of devices for RNA detection and systems for therapeutic NA cell delivery», 2013-2015 (Apartsin E.K.)

Automated synthesizers (BIOSSET, Russia); analytical and preparative chromatographs; vacuum concentrator Speed-Vac and rotavapors; equipment for electrophoresis; thermostates and thermomixers.