Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells
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 cel...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253123000744 |
| _version_ | 1827971001058590720 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Anna S. Kichkailo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T19:01:38Z |
| format | Article |
| id | doaj.art-f65de7532b0f4df1b79a409702872882 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-09T19:01:38Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-f65de7532b0f4df1b79a4097028728822023-04-08T05:11:00ZengElsevierMolecular Therapy: Nucleic Acids2162-25312023-06-0132267288Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cellsAnna S. Kichkailo0Andrey A. Narodov1Maria A. Komarova2Tatiana N. Zamay3Galina S. Zamay4Olga S. Kolovskaya5Evgeniy E. Erakhtin6Yury E. Glazyrin7Dmitry V. Veprintsev8Roman V. Moryachkov9Vladimir V. Zabluda10Irina Shchugoreva11Polina Artyushenko12Vladimir A. Mironov13Dmitry I. Morozov14Vladimir A. Khorzhevskii15Anton V. Gorbushin16Anastasia A. Koshmanova17Elena D. Nikolaeva18Igor P. Grinev19Ivan I. Voronkovskii20Daniil S. Grek21Kirill V. Belugin22Alexander A. Volzhentsev23Oleg N. Badmaev24Natalia A. Luzan25Kirill A. Lukyanenko26Georgy Peters27Ivan N. Lapin28Andrey K. Kirichenko29Petr V. Konarev30Evgeny V. Morozov31Gleb G. Mironov32Ana Gargaun33Darija Muharemagic34Sergey S. Zamay35Elena V. Kochkina36Maya A. Dymova37Tatiana E. Smolyarova38Alexey E. Sokolov39Andrey A. Modestov40Nikolay A. Tokarev41Nikolay V. Shepelevich42Anastasia V. Ozerskaya43Natalia G. Chanchikova44Alexey V. Krat45Ruslan A. Zukov46Varvara I. Bakhtina47Pavel G. Shnyakin48Pavel A. Shesternya49Valery A. Svetlichnyi50Marina M. Petrova51Ivan P. Artyukhov52Felix N. Tomilin53Maxim V. Berezovski54Prof. 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.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, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaProf. 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, RussiaProf. 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, RussiaProf. 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, RussiaKrasnoyarsk Inter-District Ambulance Hospital named after N.S. Karpovich, 17 Kurchatova, Krasnoyarsk 660062, RussiaProf. 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, RussiaFederal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, RussiaFederal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, RussiaLaboratory of Physics of Magnetic Phenomena, Kirensky Institute of Physics, 50/38 Akademgorodok, Krasnoyarsk 660036, RussiaProf. 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, RussiaProf. 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, RussiaDepartment of Chemistry, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, South KoreaNanoscience Center and Department of Chemistry, University of Jyväskylä, P.O. Box 35, Jyväskylä 40014, FinlandProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Krasnoyarsk Regional Pathology-Anatomic Bureau, 3d Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaProf. 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, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaProf. 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, RussiaKrasnoyarsk Inter-District Ambulance Hospital named after N.S. Karpovich, 17 Kurchatova, Krasnoyarsk 660062, RussiaProf. 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, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaFederal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaFederal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaProf. 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, RussiaNational Research Center Kurchatov Institute, 1 Akademika Kurchatova, Moscow 123182, RussiaLaboratory of Advanced Materials and Technology, Siberian Physical-Technical Institute of Tomsk State University, 36 Lenina, Tomsk 634050, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaNational 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, RussiaInstitute 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, RussiaDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON K1N6N5, CanadaDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON K1N6N5, CanadaDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON K1N6N5, CanadaDepartment of Molecular Electronics, Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”, 50 Akademgorodok, Krasnoyarsk 660036, RussiaSiberian Federal University, 79 Svobodny pr., Krasnoyarsk 660041, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 8 Lavrentyev Avenue, Novosibirsk 630090, RussiaFederal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, RussiaFederal 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, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaFederal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, RussiaFederal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, RussiaProf. 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, RussiaFederal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, RussiaProf. 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, RussiaProf. 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, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaLaboratory of Advanced Materials and Technology, Siberian Physical-Technical Institute of Tomsk State University, 36 Lenina, Tomsk 634050, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, RussiaLaboratory of Physics of Magnetic Phenomena, Kirensky Institute of Physics, 50/38 Akademgorodok, Krasnoyarsk 660036, Russia; Siberian Federal University, 79 Svobodny pr., Krasnoyarsk 660041, RussiaDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON K1N6N5, CanadaHere, 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.http://www.sciencedirect.com/science/article/pii/S2162253123000744MT: Oligonucleotides: Diagnostics and Biosensorsglial brain tumorastrocytomatumor imagingfluid biopsyPET/CT |
| spellingShingle | 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 Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Diagnostics and Biosensors glial brain tumor astrocytoma tumor imaging fluid biopsy PET/CT |
| title | Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells |
| title_full | Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells |
| title_fullStr | Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells |
| title_full_unstemmed | Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells |
| title_short | Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells |
| title_sort | development of dna aptamers for visualization of glial brain tumors and detection of circulating tumor cells |
| topic | MT: Oligonucleotides: Diagnostics and Biosensors glial brain tumor astrocytoma tumor imaging fluid biopsy PET/CT |
| url | http://www.sciencedirect.com/science/article/pii/S2162253123000744 |
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