Open Access

Molecular Therapy - Nucleic Acids, volume 32, pages 267-288

Development of DNA Aptamers for Visualization of Glial Brain Tumors and Detection of Circulating Tumor Cells

Kichkailo Anna S. ^{1, 2}

Narodov Andrey A ^{1, 3}

Komarova Maria A. ¹

Zamay Tatiana N. ^{1, 2}

Zamay Galina S. ^{1, 2}

Kolovskaya Olga S. ^{1, 2}

Erakhtin Evgeniy E. ³

Glazyrin Yury E. ^{1, 2}

Veprintsev Dmitry V ²

Moryachkov R V ²

Zabluda Vladimir V. ⁴

Shchugoreva Irina A ^{1, 2, 5}

Artyushenko Polina V ^{1, 2, 5}

Mironov Vladimir A. ⁶

Morozov D I ⁷

Khorzhevskii Vladimir A ^{1, 8}

Gorbushin Anton V. ^{1, 3}

Koshmanova Anastasia A. ¹

Nikolaeva Elena D. ^{1, 2}

Grinev Igor P. ³

Voronkovskii Ivan I. ^{1, 3}

Grek Daniil S. ¹

Belugin Kirill ⁹

Volzhentsev Alexander A ¹

Badmaev Oleg N ⁹

Luzan Natalia A ¹

Lukyanenko Kirill A. ^{1, 2, 5}

Peters Georgy ¹⁰

Lapin Ivan N. ¹¹

Kirichenko Andrey K ¹

Konarev Petr V. ^{10, 12}

Morozov E. V. ¹³

Mironov Gleb G ¹⁴

Gargaun Ana ¹⁴

Muharemagic Darija ¹⁴

Zamay Sergey S. ¹⁵

Kochkina Elena V ⁵

Дымова М. А. ¹⁶

Smolyarova Tatiana E ²

Sokolov I E ^{2, 4}

Modestov A.A. ¹

Tokarev Nikolay A ⁹

Shepelevich N.V. ⁹

Ozerskaya Anastasia V ^{1, 9}

Chanchikova Natalia G ⁹

Krat Alexey V. ^{1, 17}

Zukov Ruslan A. ^{1, 17}

Bakhtina V. I. ¹

Shnyakin P. G. ¹

Shesternya Pavel ¹

Svetlichnyi Valery A ¹¹

Petrova M M ¹

Artyukhov Ivan P. ¹

Tomilin Felix N. ^{4, 5}

Berezovski Maxim V. ¹⁴

Hide authors affiliations Show authors affiliations: 17 affiliations

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 |

Krasnoyarsk Inter-District Ambulance Hospital named after N.S. Karpovich, 17 Kurchatova, Krasnoyarsk 660062, Russia

National Research Centre "Kurchatov Institute"

Karpov Institute of Physical Chemistry

⁴

Laboratory of Physics of Magnetic Phenomena, Kirensky Institute of Physics, 50/38 Akademgorodok, Krasnoyarsk 660036, Russia |

⁵

Siberian Federal University, 79 Svobodny pr., Krasnoyarsk 660041, Russia |

⁶

Department of Chemistry, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, South Korea |

⁷

Nanoscience Center and Department of Chemistry, University of Jyväskylä, P.O. Box 35, Jyväskylä 40014, Finland |

⁸

Krasnoyarsk Regional Pathology-Anatomic Bureau, 3d Partizana Zheleznyaka, Krasnoyarsk 660022, Russia |

⁹

Federal Siberian Research Clinical Centre Under the Federal Medical Biological Agency, Krasnoyarsk, Russia |

¹⁰

National Research Center Kurchatov Institute, 1 Akademika Kurchatova, Moscow 123182, Russia |

¹¹

Laboratory of Advanced Materials and Technology, Siberian Physical-Technical Institute of Tomsk State University, 36 Lenina, Tomsk 634050, Russia |

¹²

A.V. Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics” RAS, 59 Leninsky pr., Moscow 119333, Russia

FSRC "Crystallography and photonics" of NRC «Kurchatov Institute»

Shubnikov Institute of Crystallography

¹³

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

Institute of Chemistry and Chemical Technology of the Siberian Branch of the Russian Academy of Sciences

Federal Research Center "Krasnoyarsk Science Center" of the Siberian Branch of the Russian Academy of Sciences

¹⁴

Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON K1N6N5, Canada |

¹⁵

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 |

¹⁶

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 8 Lavrentyev Avenue, Novosibirsk 630090, Russia |

¹⁷

Krasnoyarsk Regional Clinical Cancer Center, 16 1-ya Smolenskaya, Krasnoyarsk 660133, Russia |

Publication type: Journal Article

Publication date: 2023-06-01

Elsevier

Journal: Molecular Therapy - Nucleic Acids

Quartile SCImago

Quartile WOS

Impact factor: 8.8

ISSN: 21622531

DOI: 10.1016/j.omtn.2023.03.015

Copy DOI

PubMed ID: 37090419

Drug Discovery

Molecular Medicine

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. 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.

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Citations by journals

	1 2
Cancers	Cancers, 2, 28.57% Cancers 2 publications, 28.57%
Nature Reviews Methods Primers	Nature Reviews Methods Primers, 1, 14.29% Nature Reviews Methods Primers 1 publication, 14.29%
Biomedicines	Biomedicines, 1, 14.29% Biomedicines 1 publication, 14.29%
Siberian Journal of Oncology	Siberian Journal of Oncology, 1, 14.29% Siberian Journal of Oncology 1 publication, 14.29%
Virulence	Virulence, 1, 14.29% Virulence 1 publication, 14.29%
Molecules	Molecules, 1, 14.29% Molecules 1 publication, 14.29%
	1 2

Citations by publishers

	1 2 3 4
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 4, 57.14% Multidisciplinary Digital Publishing Institute (MDPI) 4 publications, 57.14%
Springer Nature	Springer Nature, 1, 14.29% Springer Nature 1 publication, 14.29%
Tomsk National Research Medical Center of the Russian Academy of Sciences	Tomsk National Research Medical Center of the Russian Academy of Sciences, 1, 14.29% Tomsk National Research Medical Center of the Russian Academy of Sciences 1 publication, 14.29%
Taylor & Francis	Taylor & Francis, 1, 14.29% Taylor & Francis 1 publication, 14.29%
	1 2 3 4

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GOST Copy

Kichkailo A. S. et al. Development of DNA Aptamers for Visualization of Glial Brain Tumors and Detection of Circulating Tumor Cells // Molecular Therapy - Nucleic Acids. 2023. Vol. 32. pp. 267-288.

GOST all authors (up to 50) Copy

Kichkailo A. S. et al. Development of DNA Aptamers for Visualization of Glial Brain Tumors and Detection of Circulating Tumor Cells // Molecular Therapy - Nucleic Acids. 2023. Vol. 32. pp. 267-288.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1016/j.omtn.2023.03.015

UR - https://doi.org/10.1016%2Fj.omtn.2023.03.015

TI - Development of DNA Aptamers for Visualization of Glial Brain Tumors and Detection of Circulating Tumor Cells

T2 - Molecular Therapy - Nucleic Acids

AU - Kichkailo, Anna S.

AU - Narodov, Andrey A

AU - Komarova, Maria A.

AU - Zamay, Tatiana N.

AU - Zamay, Galina S.

AU - Kolovskaya, Olga S.

AU - Erakhtin, Evgeniy E.

AU - Glazyrin, Yury E.

AU - Veprintsev, Dmitry V

AU - Moryachkov, R V

AU - Zabluda, Vladimir V.

AU - Shchugoreva, Irina A

AU - Artyushenko, Polina V

AU - Mironov, Vladimir A.

AU - Morozov, D I

AU - Khorzhevskii, Vladimir A

AU - Gorbushin, Anton V.

AU - Koshmanova, Anastasia A.

AU - Nikolaeva, Elena D.

AU - Grinev, Igor P.

AU - Voronkovskii, Ivan I.

AU - Grek, Daniil S.

AU - Belugin, Kirill

AU - Volzhentsev, Alexander A

AU - Badmaev, Oleg N

AU - Luzan, Natalia A

AU - Lukyanenko, Kirill A.

AU - Peters, Georgy

AU - Lapin, Ivan N.

AU - Kirichenko, Andrey K

AU - Konarev, Petr V.

AU - Morozov, E. V.

AU - Mironov, Gleb G

AU - Gargaun, Ana

AU - Muharemagic, Darija

AU - Zamay, Sergey S.

AU - Kochkina, Elena V

AU - Дымова, М. А.

AU - Smolyarova, Tatiana E

AU - Sokolov, I E

AU - Modestov, A.A.

AU - Tokarev, Nikolay A

AU - Shepelevich, N.V.

AU - Ozerskaya, Anastasia V

AU - Chanchikova, Natalia G

AU - Krat, Alexey V.

AU - Zukov, Ruslan A.

AU - Bakhtina, V. I.

AU - Shnyakin, P. G.

AU - Shesternya, Pavel

AU - Svetlichnyi, Valery A

AU - Petrova, M M

AU - Artyukhov, Ivan P.

AU - Tomilin, Felix N.

AU - Berezovski, Maxim V.

PY - 2023

DA - 2023/06/01 00:00:00

PB - Elsevier

SP - 267-288

VL - 32

PMID - 37090419

SN - 2162-2531

ER -

BibTex

Cite this

BibTex Copy

@article{2023_Kichkailo,

author = {Anna S. Kichkailo and Andrey A Narodov and Maria A. Komarova and Tatiana N. Zamay and Galina S. Zamay and Olga S. Kolovskaya and Evgeniy E. Erakhtin and Yury E. Glazyrin and Dmitry V Veprintsev and R V Moryachkov and Vladimir V. Zabluda and Irina A Shchugoreva and Polina V Artyushenko and Vladimir A. Mironov and D I Morozov and Vladimir A Khorzhevskii and Anton V. Gorbushin and Anastasia A. Koshmanova and Elena D. Nikolaeva and Igor P. Grinev and Ivan I. Voronkovskii and Daniil S. Grek and Kirill Belugin and Alexander A Volzhentsev and Oleg N Badmaev and Natalia A Luzan and Kirill A. Lukyanenko and Georgy Peters and Ivan N. Lapin and Andrey K Kirichenko and Petr V. Konarev and E. V. Morozov and Gleb G Mironov and Ana Gargaun and Darija Muharemagic and Sergey S. Zamay and Elena V Kochkina and М. А. Дымова and Tatiana E Smolyarova and I E Sokolov and A.A. Modestov and Nikolay A Tokarev and N.V. Shepelevich and Anastasia V Ozerskaya and Natalia G Chanchikova and Alexey V. Krat and Ruslan A. Zukov and V. I. Bakhtina and P. G. Shnyakin and Pavel Shesternya and Valery A Svetlichnyi and M M Petrova and Ivan P. Artyukhov and Felix N. Tomilin and Maxim V. Berezovski},

title = {Development of DNA Aptamers for Visualization of Glial Brain Tumors and Detection of Circulating Tumor Cells},

journal = {Molecular Therapy - Nucleic Acids},

year = {2023},

volume = {32},

publisher = {Elsevier},

month = {jun},

url = {https://doi.org/10.1016%2Fj.omtn.2023.03.015},

pages = {267--288},

doi = {10.1016/j.omtn.2023.03.015}

}

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Publisher

Elsevier

Journal

Molecular Therapy - Nucleic Acids

Quartile SCImago

Quartile WOS

Impact factor

8.8

ISSN

21622531 (Electronic)

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