Using Computer Modeling and Experimental Methods to Screen for Aptamers That Bind to the VV-GMCSF-LACT Virus
Maya Dymova,
Natalia Vasileva,
Daria Malysheva,
Alisa Ageenko,
Irina Shchugoreva,
Polina Artyushenko,
Felix Tomilin,
Anna S. Kichkailo,
Elena Kuligina,
Vladimir Richter
Affiliations
Maya Dymova
The Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia
Natalia Vasileva
The Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia
Daria Malysheva
The Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia
Alisa Ageenko
The Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia
Irina Shchugoreva
The Laboratory For Biomolecular and Medical Technologies, Krasnoyarsk State Medical University Named after Professor V.F. Voyno-Yasenetsky, 660022 Krasnoyarsk, Russia
Polina Artyushenko
The Laboratory For Biomolecular and Medical Technologies, Krasnoyarsk State Medical University Named after Professor V.F. Voyno-Yasenetsky, 660022 Krasnoyarsk, Russia
Felix Tomilin
The Laboratory for Digital Controlled Drugs and Theranostics, Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”, 660036 Krasnoyarsk, Russia
Anna S. Kichkailo
The Laboratory For Biomolecular and Medical Technologies, Krasnoyarsk State Medical University Named after Professor V.F. Voyno-Yasenetsky, 660022 Krasnoyarsk, Russia
Elena Kuligina
The Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia
Vladimir Richter
The Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia
Oncolytic virotherapy is a promising approach for cancer treatment. However, when introduced into the body, the virus provokes the production of virus-neutralizing antibodies, which can reduce its antitumor effect. To shield viruses from the immune system, aptamers that can cover the membrane of the viral particle are used. Aptamers that specifically bind to the JX-594 strain of the vaccinia virus were developed earlier. However, the parameters for binding to the recombinant virus VV-GMCSF-Lact, developed based on the LIVP strain of the vaccinia virus, may differ due its different repertoire of antigenic determinants on its membrane compared to JX-594. In this work, the spatial atomic structures of aptamers to JX-594 and bifunctional aptamers were determined using molecular modeling. The efficiency of viral particles binding to the aptamers (EC50), as well as the cytotoxicity and stability of the aptamers were studied. The synergistic effect of the VV-GMCSF-Lact combination with the aptamers in the presence of serum was investigated using human glioblastoma cells. This proposed approach allowed us to conduct a preliminary screening of sequences using in silico modeling and experimental methods, and identified potential candidates that are capable of shielding VV-GMCSF-Lact from virus-neutralizing antibodies.
