Molecular Therapy: Nucleic Acids (Jun 2023)
Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells
- Anna S. Kichkailo,
- Andrey A. Narodov,
- Maria A. Komarova,
- Tatiana N. Zamay,
- Galina S. Zamay,
- Olga S. Kolovskaya,
- Evgeniy E. Erakhtin,
- Yury E. Glazyrin,
- Dmitry V. Veprintsev,
- Roman V. Moryachkov,
- Vladimir V. Zabluda,
- Irina Shchugoreva,
- Polina Artyushenko,
- Vladimir A. Mironov,
- Dmitry I. Morozov,
- Vladimir A. Khorzhevskii,
- Anton V. Gorbushin,
- Anastasia A. Koshmanova,
- Elena D. Nikolaeva,
- Igor P. Grinev,
- Ivan I. Voronkovskii,
- Daniil S. Grek,
- Kirill V. Belugin,
- Alexander A. Volzhentsev,
- Oleg N. Badmaev,
- Natalia A. Luzan,
- Kirill A. Lukyanenko,
- Georgy Peters,
- Ivan N. Lapin,
- Andrey K. Kirichenko,
- Petr V. Konarev,
- Evgeny V. Morozov,
- Gleb G. Mironov,
- Ana Gargaun,
- Darija Muharemagic,
- Sergey S. Zamay,
- Elena V. Kochkina,
- Maya A. Dymova,
- Tatiana E. Smolyarova,
- Alexey E. Sokolov,
- Andrey A. Modestov,
- Nikolay A. Tokarev,
- Nikolay V. Shepelevich,
- Anastasia V. Ozerskaya,
- Natalia G. Chanchikova,
- Alexey V. Krat,
- Ruslan A. Zukov,
- Varvara I. Bakhtina,
- Pavel G. Shnyakin,
- Pavel A. Shesternya,
- Valery A. Svetlichnyi,
- Marina M. Petrova,
- Ivan P. Artyukhov,
- Felix N. Tomilin,
- Maxim V. Berezovski
Affiliations
- Anna S. Kichkailo
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia; Corresponding author: Anna S. Kichkailo, Laboratory for Biomolecular and Medical Technologies, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia.
- Andrey A. Narodov
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Krasnoyarsk Inter-District Ambulance Hospital named after N.S. Karpovich, 17 Kurchatova, Krasnoyarsk 660062, Russia
- Maria A. Komarova
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Tatiana N. Zamay
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia
- Galina S. Zamay
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia
- Olga S. Kolovskaya
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia
- Evgeniy E. Erakhtin
- Krasnoyarsk Inter-District Ambulance Hospital named after N.S. Karpovich, 17 Kurchatova, Krasnoyarsk 660062, Russia
- Yury E. Glazyrin
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia
- Dmitry V. Veprintsev
- Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia
- Roman V. Moryachkov
- Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia
- Vladimir V. Zabluda
- Laboratory of Physics of Magnetic Phenomena, Kirensky Institute of Physics, 50/38 Akademgorodok, Krasnoyarsk 660036, Russia
- Irina Shchugoreva
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia; Siberian Federal University, 79 Svobodny pr., Krasnoyarsk 660041, Russia
- Polina Artyushenko
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia; Siberian Federal University, 79 Svobodny pr., Krasnoyarsk 660041, Russia
- Vladimir A. Mironov
- Department of Chemistry, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, South Korea
- Dmitry I. Morozov
- Nanoscience Center and Department of Chemistry, University of Jyväskylä, P.O. Box 35, Jyväskylä 40014, Finland
- Vladimir A. Khorzhevskii
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Krasnoyarsk Regional Pathology-Anatomic Bureau, 3d Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Anton V. Gorbushin
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Krasnoyarsk Inter-District Ambulance Hospital named after N.S. Karpovich, 17 Kurchatova, Krasnoyarsk 660062, Russia
- Anastasia A. Koshmanova
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Elena D. Nikolaeva
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia
- Igor P. Grinev
- Krasnoyarsk Inter-District Ambulance Hospital named after N.S. Karpovich, 17 Kurchatova, Krasnoyarsk 660062, Russia
- Ivan I. Voronkovskii
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Krasnoyarsk Inter-District Ambulance Hospital named after N.S. Karpovich, 17 Kurchatova, Krasnoyarsk 660062, Russia
- Daniil S. Grek
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Kirill V. Belugin
- Federal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, Russia
- Alexander A. Volzhentsev
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Oleg N. Badmaev
- Federal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, Russia
- Natalia A. Luzan
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Kirill A. Lukyanenko
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia; Siberian Federal University, 79 Svobodny pr., Krasnoyarsk 660041, Russia
- Georgy Peters
- National Research Center Kurchatov Institute, 1 Akademika Kurchatova, Moscow 123182, Russia
- Ivan N. Lapin
- Laboratory of Advanced Materials and Technology, Siberian Physical-Technical Institute of Tomsk State University, 36 Lenina, Tomsk 634050, Russia
- Andrey K. Kirichenko
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Petr V. Konarev
- National Research Center Kurchatov Institute, 1 Akademika Kurchatova, Moscow 123182, Russia; A.V. Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics” RAS, 59 Leninsky pr., Moscow 119333, Russia
- Evgeny V. Morozov
- Institute of Chemistry and Chemical Technology SB RAS – The Branch of Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”, Krasnoyarsk 660036, Russia
- Gleb G. Mironov
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON K1N6N5, Canada
- Ana Gargaun
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON K1N6N5, Canada
- Darija Muharemagic
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON K1N6N5, Canada
- Sergey S. Zamay
- Department of Molecular Electronics, Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”, 50 Akademgorodok, Krasnoyarsk 660036, Russia
- Elena V. Kochkina
- Siberian Federal University, 79 Svobodny pr., Krasnoyarsk 660041, Russia
- Maya A. Dymova
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 8 Lavrentyev Avenue, Novosibirsk 630090, Russia
- Tatiana E. Smolyarova
- Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia
- Alexey E. Sokolov
- Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia; Laboratory of Physics of Magnetic Phenomena, Kirensky Institute of Physics, 50/38 Akademgorodok, Krasnoyarsk 660036, Russia
- Andrey A. Modestov
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Nikolay A. Tokarev
- Federal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, Russia
- Nikolay V. Shepelevich
- Federal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, Russia
- Anastasia V. Ozerskaya
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Federal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, Russia
- Natalia G. Chanchikova
- Federal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, Russia
- Alexey V. Krat
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Krasnoyarsk Regional Clinical Cancer Center, 16 1-ya Smolenskaya, Krasnoyarsk 660133, Russia
- Ruslan A. Zukov
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Krasnoyarsk Regional Clinical Cancer Center, 16 1-ya Smolenskaya, Krasnoyarsk 660133, Russia
- Varvara I. Bakhtina
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Pavel G. Shnyakin
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Pavel A. Shesternya
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Valery A. Svetlichnyi
- Laboratory of Advanced Materials and Technology, Siberian Physical-Technical Institute of Tomsk State University, 36 Lenina, Tomsk 634050, Russia
- Marina M. Petrova
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Ivan P. Artyukhov
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
- Felix N. Tomilin
- Laboratory of Physics of Magnetic Phenomena, Kirensky Institute of Physics, 50/38 Akademgorodok, Krasnoyarsk 660036, Russia; Siberian Federal University, 79 Svobodny pr., Krasnoyarsk 660041, Russia
- Maxim V. Berezovski
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON K1N6N5, Canada
- Journal volume & issue
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Vol. 32
pp. 267 – 288
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.
