Laboratory of Nucleic Acids Chemistry

Phone: +7(383) 363-51-24

• Development of methods for delivery of drugs based on DNA fragments, peptide nucleic acids (PNA), antibiotics, nucleoside triphosphate analogs into cells using biocompatible and nanomaterials of low toxicity.
• Design of innovative DNA-based drugs for highly-selective and efficient action on nucleic acids in cells as target. Development of virus-specific agents consisting of nanoparticles conjugated with DNAzymes, oligonucleotides, and peptide nucleic acids.
• Design of nanocomposites based on nanoparticles and antibiotic bleomycin A5 capable of penetrating into cells and damaging intracellular nucleic acids.
• Development and investigation of agents based on nanoparticles conjugated with nucleoside triphosphate analogs.
• Development of new approaches for efficient and selective regulation of interaction between oligonucleotides and nucleic acids.

• For the first time the principle of complementary-addressed modification of nucleic acids was formulated. This principle became the basis of a new scientific field, so called antisense technology. The priority in this field was officially confirmed by scientific society (1998).
• New reactions and relationships were revealed while studying of mechanism of oligonucleotide synthesis and other phosphorylation reactions. This work was awarded by the Shemyakin Prize (1999).
• Original efficient and simple method of the attachment of various chemical groups to the terminal phosphates of deblocked deoxyribo- and ribooligonucleotides and their analogs was developed; a wide spectrum of new compounds with different action on nucleic acids were synthesized (alkylating, photo-cross-linking, stabilizing, damaging derivatives of oligonucleotides, enhancing their penetration into cells, etc.). For the first time the conjugates of oligonucleotides with steroids were synthesized, which penetrate more efficiently into cells than other oligonucleotide derivatives. The method is widely used by Russian and foreign researches. This work was awarded by the State prize of Russian Federation (1999).
• Original approach to enhance the efficiency and selectivity of complementary modification of nucleic acids was developed with the use of short oligonucleotide reagents flanked by auxiliary oligonucleotides (effectors). The method is based on use of mini-probes, i.e. tandems of short oligonucleotides or tandems of linked with a non-nucelotide spacer. Using proposed approach, we developed test systems for revealing and genotyping hepatitis C virus (HCV). The proposed mini-probes showed themselves as prospective tools for detection, revealing and genotyping drug-resistant forms of viruses. The proposed method has no analogs in Russia and abroad. The developed conception for revealing significant one-nucleotide substitutions (SNP) was used for genotyping Y chromosome.
• The system for delivery of DNA and PNA fragments into cells was developed using nanomaterials. The prepared nanocomposites consisting of titanium dioxide nanoparticles and DNA fragments appeared to be low toxic for cells (ТС50 ≈ 1800 mcg/ml) and very efficient against influenza A virus (99.99 % inhibition of virus reproduction). These nanocomposites can be considered as prospective compounds for investigations in functional genomics and preparation of drugs for treatment and prophylaxis of viral and other diseases associated with functioning nucleic acids.
• Efficient method of immobilization of oligonucleotides onto glass and other surfaces was elaborated to fabricate DNA chips.

1. Levina A.S., Repkova M.N., Ismagilov Z.R., Shikina N.V., Mazurkova N.A., Zarytova V.F. Efficient Inhibition of Human Influenza A Virus by Oligonucleotides Electrostatically Fixed on Polylysine Containing TiO2 Nanoparticles. Russ. J. of Bioorg. Chem. 2014. 40, 196 202.
2. Amirkhanov N.V., Zarytova V.F., Amirkhanov R.N. Composites of peptide nucleic acids with titanium dioxide nanoparticles. III. Dissocoation kinetics of PNA from nanocomposites containing DNA/PNA duplexes. Russ. J. of Bioorg. Chem. 2014. 40, 286-292.
3. Amirkhanov N.V., Zarytova V.F., Amirkhanov R.N. Composites of peptide nucleic acids with titanium dioxide nanoparticles. II. Dissociation of DNA/PNA duplexes in nanocompositesTiO2-polylysine-DNA/PNA and in solution. Effect of polylsyisne. Russ. J. of Bioorg. Chem. 2013. 39, 705-717.
4. Shatskaya N.V., Levina A.S., Repkova M.N., Baiborodin S.I., Shikina N.V., Ismagilov Z.R., Zarytova V.F. Delivery of Bleomycin A5 into Cells Using TiO2 Nanoparticles to Enhance the Degradation of Intracellular DNA. Nanotechnologies in Russia. 2013. 8(3-4), 87-91.
5. Vasilyeva S.V., Silnikov V.N., Shatskaya N.V., Levina A.S., Repkova M.N., Zarytova V.F. SiO2 Nanoparticles as platform for delivery of nucleoside triphosphates analogues into cells. Bioorg. Med. Chem. 2013. 21(3), 703-711.
6. Evdokimov А.А., Mazurkova N.A., Malygin E.G., Zarytova V.F., Levina A.S., Repkova M.N., Zagrebelnyi S.N., Netesova N.A. Design of Deoxyribozymes for Inhibition of Influenza A Virus Reproduction. Molecular Biology (Moscow). 2013. 47(1), 83-93.
7. Mikhailov V.S., Potapov V.K., Amirkhanov N.V., Amirkhanov R.N., Bulanenkova S.S., Akopov S.B., Zarytova V.F., Nikolaev L.G., Sverdlov E.D. Affinity uptake of given DNA fragments using short synthetic sequences. Russ. J. of Bioorg. Chem. 2013. 39(1), 81.
8. Levina A.S., Ismagilov Z.R., Repkova M.N., Shikina N.V., Baiborodin S.I., Shatskaya N.V., Zagrebelnyi S.N., Zarytova V.F.. Design of TiO2~DNA Nanocomposites for Penetration into Cells. Russ. J. of Bioorg. Chem. 2013. 39(1), 87–98.
9. Levina A.S., Repkova M.N., Ismagilov Z.R, Shikina N.V., Malygin E.G, Mazurkova N.A., Zinov’ev V.V., Evdokimov A.A., Baiborodin S.I., Zarytova V.F. High-performance method for specific effect on nucleic acids in cells using TiO2~DNA nanocomposites. Scientific Reports. 2012. 2, a756.
10. Levina A., Ismagilov Z., Repkova M., Shatskaya N., Shikina N., Tusikov F., Zarytova V., Nanocomposites consisting of titanium dioxide nanoparticles and oligonucleotides. Journal of Nanoscience and Nanotechnology. 2012. 12, 1812-1820.
11. Amirkhanov R.N, Amirkhanov N.V., Zarytova V.F. Composites of peptide nucleic acids with titanium dioxide nanoparticles. I. Design of nanocomposites containing DNA/PNA duplexes and their delivery into HeLa cells. Russ. J. of Bioorg. Chem. 2012. 38, 692-705.
12. Ismagilov Z.R., Shikina N.V., Bessudnova E.V., Levina A.S., Repkova M.N., Ryabchikova E.I., Tuzikov F.V., Vladimirova A.V., Zagrebelnyi S.N., Zarytova V.F. Design and investigation of properties of nanocomposites based on TiO2 nanoparticles containing DNA fragments. Nanotechnika. 2012. 2, 76-84.
13. Amirkhanov R.N, Zarytova V.F., Amirkhanov N.V. Smart titanium dioxide nanocomposites for cellular delivery of the antisense peptide nucleic acids. Smart Nanocomposites. 2011. Nova Science Publishers, Inc., NY, 2(1), 29-38. ISSN: 1949 4823.
14. Fedorinin V.N., Paulish A.G., Levina A.S., Zarytova V.F. Optoelectronics in Measurement of Physical Magnitudes. In: “Advances in Electrical Engineering Research” (Ed. T.M. Brouwer, Nova Science Publishers, Inc., NY). 2011. 1, 185-226. ISBN: 978-1-61728-496-0.

1. Zarytova V.F., Levina A.S., Repkova M.N., Ismagilov Z.R., Shikina N.V. Method for obtaining nanosized delivery system of fragments of nucleic acids and their analogues to cells of mammals. Patent RF N.2499045, 2013.
2. Zarytova V.F., Ismagilov Z.R., Levina A.S., Repkova M.N., Shikina N.V., Zagrebel’nyi S.N., Mazurkova N.A. Nanocomposite with active ligand, method of its preparation and method of address inactivation of flu virus inside cell. Patent RF N.2496878, 2013.
3. Netesova N.A., Evdokimov A.A., Mazurkova N.A., Zarytova V.F., Levina A.S., Repkova M.N., Ismagilov Z.R., Shikina N.V., Zagrebelnyi S.N. Inhibitor of influenza A virus reproduction using complex of titanium dioxide nanoparticles and oligonucleotide. Patent RF N.2466188, 2012.
4. Zarytova V.F., Levina A.S., Shatskaya N.V., Repkova M.N., Ismagilov Z.R., Shikina N.V., Method of preparation of nanosystem for delivery of antibiotics of bleomycin series into mammalian cells. Patent RF N.2458705, 2012.
5. Ismagilov Z.R., Shikina N.V., Gavrilova A.A., Parmon V.N., Zarytova V.F., Levina A.S., Repkova M.N. et. al. Titanium dioxide nanocomposites for intracellular viral genome inactivation, method for making them. Patent RF N.2444571, 2012.

RFBR (Grants of Russian Foundation for Basic Research)

• N.14-04-00753 “Address impact on the nucleic acids in the cell using nanobiocomposites based on deoxyribozymes” (2014-2016)

Peptide synthesizer; chromatograph Waters 600E for HPLC; spectrophotometer UV-1800 equipped with TMSPC-8 attachment for the analysis of melting temperatures of nucleic acid complexes.