Using Computer Modeling and Experimental Methods to Screen for Aptamers That Bind to the VV-GMCSF-LACT Virus.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Aptamers, Nucleotide*/chemistry ; Aptamers, Nucleotide*/pharmacology ; Vaccinia virus*/genetics; Humans ; Cell Line, Tumor ; Computer Simulation ; Oncolytic Virotherapy/methods ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor/chemistry ; Models, Molecular ; Oncolytic Viruses/genetics ; Oncolytic Viruses/metabolism

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.

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22-64-00041 the Russian Science Foundation

Keywords: FMO-DFTB; aptamer; cytofluorimetry; microscale thermophoresis; molecular dynamics; oncolytic virus VV-GMCSF-Lact; quantum chemical calculations

0 (Aptamers, Nucleotide)
83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)

Date Created: 20241127 Date Completed: 20241127 Latest Revision: 20241130

20241202

PMC11597249

10.3390/molecules29225424

39598813