Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact

Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact

Aptamers are currently being investigated for their potential to improve virotherapy. They offer several advantages, including the ability to prevent the aggregation of viral particles, enhance target specificity, and protect against the neutralizing effects of antibodies. The purpose of this study...

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Published in:Molecules (Basel, Switzerland) Vol. 29; no. 4; p. 848
Main Authors: Dymova, Maya A, Malysheva, Daria O, Popova, Victoria K, Dmitrienko, Elena V, Endutkin, Anton V, Drokov, Danil V, Mukhanov, Vladimir S, Byvakina, Arina A, Kochneva, Galina V, Artyushenko, Polina V, Shchugoreva, Irina A, Rogova, Anastasia V, Tomilin, Felix N, Kichkailo, Anna S, Richter, Vladimir A, Kuligina, Elena V
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 01-02-2024
MDPI
Subjects:
Antibodies
Antibodies, Neutralizing
aptamer
Aptamers, Nucleotide - metabolism
Biological products
Brain cancer
Brain tumors
Chemotherapy
Computer software industry
dynamic light scattering
Flow cytometry
Glioma
Gliomas
Health aspects
Humans
Immune system
Immunotherapy
microscale thermophoresis
Mortality
oncolytic virus
Oncolytic Viruses
Radiation therapy
Russia
Simulation
United States
Vaccinia virus - genetics
Viral antibodies
Viruses
United States
Russia
microscale thermophoresis
glioma
dynamic light scattering
aptamer
oncolytic virus
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Summary:Aptamers are currently being investigated for their potential to improve virotherapy. They offer several advantages, including the ability to prevent the aggregation of viral particles, enhance target specificity, and protect against the neutralizing effects of antibodies. The purpose of this study was to comprehensively investigate an aptamer capable of enhancing virotherapy. This involved characterizing the previously selected aptamer for vaccinia virus (VACV), evaluating the aggregation and molecular interaction of the optimized aptamers with the recombinant oncolytic virus VV-GMCSF-Lact, and estimating their immunoshielding properties in the presence of human blood serum. We chose one optimized aptamer, NV14t_56, with the highest affinity to the virus from the pool of several truncated aptamers and built its 3D model. The NV14t_56 remained stable in human blood serum for 1 h and bound to VV-GMCSF-Lact in the micromolar range (Kd ≈ 0.35 μM). Based on dynamic light scattering data, it has been demonstrated that aptamers surround viral particles and inhibit aggregate formation. In the presence of serum, the hydrodynamic diameter (by intensity) of the aptamer-virus complex did not change. Microscale thermophoresis (MST) experiments showed that NV14t_56 binds with virus (EC50 = 1.487 × 10 PFU/mL). The analysis of the amplitudes of MST curves reveals that the components of the serum bind to the aptamer-virus complex without disrupting it. In vitro experiments demonstrated the efficacy of VV-GMCSF-Lact in conjunction with the aptamer when exposed to human blood serum in the absence of neutralizing antibodies (Nabs). Thus, NV14t_56 has the ability to inhibit virus aggregation, allowing VV-GMCSF-Lact to maintain its effectiveness throughout the storage period and subsequent use. When employing aptamers as protective agents for oncolytic viruses, the presence of neutralizing antibodies should be taken into account.
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ISSN:1420-3049
1420-3049
DOI:10.3390/molecules29040848