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Using Computer Modeling and Experimental Methods to Screen for Aptamers That Bind to the VV-GMCSF-LACT Virus
Maya Dymova1, Natalia Vasileva1, Daria Malysheva1
1The Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia.
Abstract:
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.
Insights
Aptamers can shield oncolytic viruses from neutralizing antibodies, enhancing cancer therapy. This study identified aptamer candidates to protect VV-GMCSF-Lact viruses, improving their effectiveness.
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Oncolytic virotherapy shows promise for cancer treatment but is limited by virus-neutralizing antibodies.
- Aptamers can shield viruses from the immune system, but their efficacy depends on the specific viral strain.
Purpose of the Study:
- To develop and evaluate aptamers for shielding the VV-GMCSF-Lact vaccinia virus strain from neutralizing antibodies.
- To investigate the binding efficiency, cytotoxicity, and stability of aptamers against VV-GMCSF-Lact.
- To assess the synergistic effect of aptamer-shielded VV-GMCSF-Lact with human glioblastoma cells.
Main Methods:
- Molecular modeling to determine aptamer structures.
- In vitro studies to measure aptamer binding efficiency (EC50), cytotoxicity, and stability.
- Co-culture experiments with human glioblastoma cells to evaluate synergistic effects in serum.
Main Results:
- Spatial atomic structures of aptamers were determined using molecular modeling.
- Aptamer binding efficiency, cytotoxicity, and stability were characterized.
- Preliminary screening identified potential aptamer candidates capable of shielding VV-GMCSF-Lact from neutralizing antibodies.
Conclusions:
- A combined in silico and experimental approach enables preliminary screening of aptamer candidates.
- Identified aptamers show potential for protecting VV-GMCSF-Lact from immune neutralization, enhancing oncolytic virotherapy effectiveness.
