A1 Journal article (refereed)
Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells (2023)

Kichkailo, A. S., Narodov, A. A., Komarova, M. A., Zamay, T. N., Zamay, G. S., Kolovskaya, O. S., Erakhtin, E. E., Glazyrin, Y. E., Veprintsev, D. V., Moryachkov, R. V., Zabluda, V. V., Shchugoreva, I., Artyushenko, P., Mironov, V. A., Morozov, D. I., Khorzhevskii, V. A., Gorbushin, A. V., Koshmanova, A. A., Nikolaeva, E. D., . . . Berezovski, M. V. (2023). Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells. Molecular Therapy Nucleic Acids, 32, 267-288. https://doi.org/10.1016/j.omtn.2023.03.015

JYU authors or editors

Publication details

All authors or editors: Kichkailo, Anna S.; Narodov, Andrey A.; Komarova, Maria A.; Zamay, Tatiana N.; Zamay, Galina S.; Kolovskaya, Olga S.; Erakhtin, Evgeniy E.; Glazyrin, Yury E.; Veprintsev, Dmitry V.; Moryachkov, Roman V.; et al.

Journal or series: Molecular Therapy Nucleic Acids

eISSN: 2162-2531

Publication year: 2023

Publication date: 24/03/2023

Volume: 32

Pages range: 267-288

Publisher: Elsevier BV

Publication country: United States

Publication language: English

DOI: https://doi.org/10.1016/j.omtn.2023.03.015

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/86530

Additional information: NGS sequencing data are deposited at https://drive.google.com/file/d/1adu9ZphI-LJv0EnvIqTonQ7j112VheZS/view?usp=share_link. SAXS data and associated files are available from the SASBDB database (www.sasbdb.org), SASBDB: SASDRY7, SASDPZ8. Mass Spectrometry Data: Glazyrin, Yury (2022), “Mass Spectrometry Data,” Mendeley Data: https://doi.org/10.17632/nvn5spksw8.1 Any other data are available upon request.

Abstract

Here, we present DNA aptamers capable of specific binding to glial tumor cells in vitro, ex vivo, and in vivo for visualization diagnostics of central nervous system tumors. We selected the aptamers binding specifically to the postoperative human glial primary tumors and not to the healthy brain cells and meningioma, using a modified process of systematic evolution of ligands by exponential enrichment to cells; sequenced and analyzed ssDNA pools using bioinformatic tools and identified the best aptamers by their binding abilities; determined three-dimensional structures of lead aptamers (Gli-55 and Gli-233) with small-angle X-ray scattering and molecular modeling; isolated and identified molecular target proteins of the aptamers by mass spectrometry; the potential binding sites of Gli-233 to the target protein and the role of post-translational modifications were verified by molecular dynamics simulations. The anti-glioma aptamers Gli-233 and Gli-55 were used to detect circulating tumor cells in liquid biopsies. These aptamers were used for in situ, ex vivo tissue staining, histopathological analyses, and fluorescence-guided tumor and PET/CT tumor visualization in mice with xenotransplanted human astrocytoma. The aptamers did not show in vivo toxicity in the preclinical animal study. This study demonstrates the potential applications of aptamers for precise diagnostics and fluorescence-guided surgery of brain tumors.

Keywords: tumours; cancer cells; visualisation; tracers (indicators); DNA

Contributing organizations

Ministry reporting: Yes

VIRTA submission year: 2023

JUFO rating: 1