Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells

Kichkailo, Anna S.; Narodov, A. A.; Komarova, Maria A.; Zamay, Tatiana N.; Zamay, Galina S.; Kolovskaya, Olga S.; Erakhtin, E. E.; Glazyrin, Yury E.; Veprintsev, Dmitry V.; Moryachkov, Roman V.; Zabluda, Vladimir V.; Shchugoreva, Irina A.; Artyushenko, P. V.; Mironov, Vladimir; Morozov, Dmitry; Khorzhevskii, V.A.; Gorbushin, Anton V.; Koshmanova, Anastasia A.; Nikolaeva, Elena D.; Grinev, Igor P.; Voronkovskii, Ivan I.; Grek, Daniil S.; Belugin, Kirill; Volzhentsev, Alexander A.; Badmaev, Oleg N.; Luzan, Natalia; Lukyanenko, Kirill A.; Peters, G. S.; Лапин, И. Н.; Кириченко, А. К.; Konarev, Petr V.; Morozov, Evgeny V.; Mironov, Gleb G.; Gargaun, Ana; Muharemagic, Darija; Zamay, Sergey S.; Kochkina, Elena V.; Дымова, М. А.; Smolyarova, T. E.; Sokolov, A. E.; Модестов, А. А.; Tokarev, Nikolay А.; Шепелевич, Н. В.; Ozerskaya, A. V.; Chanchikova, N. G.; Krat, Alexey V.; Zukov, Ruslan; Bakhtina, Varvara I.; Shnyakin, P. G.; Shesternya, P. А.; Светличный, В. А.; Петрова, М. М.; Artyukhov, Ivan; Tomilin, Felix N.; Berezovski, Maxim V.

doi:10.1016/j.omtn.2023.03.015

Cited by 9 publications

(8 citation statements)

References 69 publications

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“…[ 26 ]. However, when using them in situ, this time is quite sufficient for diagnosing tumor cells [ 27 ]. The binding assay ( Figure 3 ) showed that the aptamer NV14t_56 bound with medium affinity to VV-GMCSF-Lact in the micromolar range (Kd = 0.3528 μM).…”

Section: Discussionmentioning

confidence: 99%

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

Dymova,

Malysheva,

Popova

et al. 2024

Molecules

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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.

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Section: Discussionmentioning

confidence: 99%

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

Dymova,

Malysheva,

Popova

et al. 2024

Molecules

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“…Previously we reported Gli-233 and Gli-55 aptamers [5] that selectively bind glial tumos. The secondary and tertiary structure of of this aptamers have been obtained using the combination of Small Angle X-Ray Scattering (SAXS) and molecular modeling.…”

Section: Modification Of Gli-233 and Gli-35 Aptamersmentioning

confidence: 99%

“…To overcome the aforementioned issues, non-specific fluorophores should be conjugated with tumor-specific ligands such as antibodies, peptides, or aptamers [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…The study demonstrates the potential use of Gli-233nt and Gli-55_3L aptamers, as well as an analog (indocyanine green spectral equivalent) Cyanin 7.5 (Cy 7.5) fluorophore, for postoperative tissue and animal model imaging. Gli-233nt and Gli-55_3L aptamers were obtained by improving the tertiary structure of the published Gli-233 and Gli-55 aptamers targeting alpha-tubulin and GFAB proteins [5]. It was shown that the generated aptamers exhibit higher affinity compared to the previous ones.…”

Section: Introductionmentioning

confidence: 99%

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Visualization of Glioblastoma with Infrared-Labeled Aptamers for Fluorescent Guided Surgery

Zamay,

Koshmanova,

Narodov

et al. 2023

Preprint

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Background: Glioblastoma remains a challenging brain tumor to treat due to its infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful tumor resection. This study introduces an innovative intraoperative visualization method utilizing a surgical fluorescence microscope to precisely locate tumor cells. The focus of the study is on IR-Glint, a novel preparation comprising Cy7.5-labeled aptamers Gli-233nt and Gli-55_3L specific to human glioblastoma. Methods: The aptamers were modified using molecular modeling and quantum chemical techniques. The effectiveness of the preparation was assessed using flow cytometry and microscopy on primary cultures of human glioblastoma. In vivo studies were conducted on mouse and rabbit models, employing orthotopic xenotransplantation of human brain glioblastoma with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. Results: The experiments validated the potential of IR-Glint for intraoperative visualization of glioblastoma using infrared imaging. Surface application of the aptamer-based formulation on the brain allowed clear visualization of the tumor, aiding surgeons in tumor resection. This approach also reduces the dosage required and mitigates potential toxic effects on the patient. Conclusions: This study demonstrates the promising potential of using in-frared dye-labeled aptamers for intraoperative visualization of glioblastoma. By improving surgical treatment outcomes in neurosurgery, this novel approach may pave the way for future advancements in the field.

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“…The distribution of matrix metalloproteinase-14 on the cell membrane was characterized by combining the aptamer probe and dSTORM [ 19 ]. DNA aptamers that bind to glial tumour cells can be used for fluorescence-guided surgery of brain tumours [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Nervous necrosis virus induced vacuolization is a Rab5- and actin-dependent process

Liu,

Wang,

Zhang

et al. 2024

Virulence

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Cytoplasmic vacuolization is commonly induced by bacteria and viruses, reflecting the complex interactions between pathogens and the host. However, their characteristics and formation remain unclear. Nervous necrosis virus (NNV) infects more than 100 global fish species, causing enormous economic losses. Vacuolization is a hallmark of NNV infection in host cells, but remains a mystery. In this study, we developed a simple aptamer labelling technique to identify red-spotted grouper NNV (RGNNV) particles in fixed and live cells to explore RGNNV-induced vacuolization. We observed that RGNNV-induced vacuolization was positively associated with the infection time and virus uptake. During infection, most RGNNV particles, as well as viral genes, colocalized with vacuoles, but not giant vacuoles > 3 μm in diameter. Although the capsid protein (CP) is the only structural protein of RGNNV, its overexpression did not induce vacuolization, suggesting that vacuole formation probably requires virus entry and replication. Given that small Rab proteins and the cytoskeleton are key factors in regulating cellular vesicles, we further investigated their roles in RGNNV-induced vacuolization. Using live cell imaging, Rab5, a marker of early endosomes, was continuously located in vacuoles bearing RGNNV during giant vacuole formation. Rab5 is required for vacuole formation and interacts with CP according to siRNA interference and Co-IP analysis. Furthermore, actin formed distinct rings around small vacuoles, while vacuoles were located near microtubules. Actin, but not microtubules, plays an important role in vacuole formation using chemical inhibitors. These results provide valuable insights into the pathogenesis and control of RGNNV infections.

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Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells

Cited by 9 publications

References 69 publications

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

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

Visualization of Glioblastoma with Infrared-Labeled Aptamers for Fluorescent Guided Surgery

Nervous necrosis virus induced vacuolization is a Rab5- and actin-dependent process

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