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

Описание

Тип публикации: статья из журнала

Год издания: 2024

Идентификатор DOI: 10.3390/molecules29225424

Ключевые слова: aptamer, oncolytic virus VV-GMCSF-Lact, microscale thermophoresis, cytofluorimetry, molecular dynamics, quantum chemical calculations, FMO-DFTB

Аннотация: <jats:p>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.Показать полностьюAptamers 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.</jats:p>

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Издание

Журнал: Molecules

Выпуск журнала: Т. 29, 22

Номера страниц: 5424

ISSN журнала: 14203049

Издатель: MDPI

Персоны

  • Dymova Maya (Institute of Chemical Biology and Fundamental Medicine SB RAS)
  • Vasileva Natalia (Institute of Chemical Biology and Fundamental Medicine SB RAS)
  • Malysheva Daria (Institute of Chemical Biology and Fundamental Medicine SB RAS)
  • Ageenko Alisa (Institute of Chemical Biology and Fundamental Medicine SB RAS)
  • Shchugoreva Irina (Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”)
  • Artyushenko Polina (Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”)
  • Tomilin Felix (L.V. Kirensky Institute of Physics SB RAS)
  • Kichkailo Anna S. (Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”)
  • Kuligina Elena (Institute of Chemical Biology and Fundamental Medicine SB RAS)
  • Richter Vladimir (Institute of Chemical Biology and Fundamental Medicine SB RAS)

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