Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact. / Dymova, Maya A.; Malysheva, Daria O.; Popova, Victoria K. и др.
в: Molecules, Том 29, № 4, 848, 08.03.2024.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact
AU - Dymova, Maya A.
AU - Malysheva, Daria O.
AU - Popova, Victoria K.
AU - Dmitrienko, Elena V.
AU - Endutkin, Anton V.
AU - Drokov, Danil V.
AU - Mukhanov, Vladimir S.
AU - Byvakina, Arina A.
AU - Kochneva, Galina V.
AU - Artyushenko, Polina V.
AU - Shchugoreva, Irina A.
AU - Rogova, Anastasia V.
AU - Tomilin, Felix N.
AU - Kichkailo, Anna S.
AU - Richter, Vladimir A.
AU - Kuligina, Elena V.
N1 - This study was supported by the Russian Science Foundation grant No. 22-64-00041. This work was supported by the Russian state-funded project for ICBFM SB RAS (grant number 121030200173-6).
PY - 2024/3/8
Y1 - 2024/3/8
N2 - 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 × 109 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.
AB - 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 × 109 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.
KW - aptamer
KW - dynamic light scattering
KW - glioma
KW - microscale thermophoresis
KW - oncolytic virus
UR - https://www.webofscience.com/wos/woscc/full-record/WOS:001172684700001
UR - https://www.mendeley.com/catalogue/3059c64b-a872-3749-933a-76505cd4b9e9/
U2 - 10.3390/molecules29040848
DO - 10.3390/molecules29040848
M3 - Article
C2 - 38398600
VL - 29
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 4
M1 - 848
ER -
ID: 61245557