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Journal articles
Targeting hormone refractory prostate cancer by $in\ vivo$ selected DNA libraries in an orthotopic xenograft mouse model
Laia Civit
1
Ioanna Theodorou
2, 3
Franziska Frey
1
Holger Weber
4
Andreas Lingnau
4
Carsten Gröber
5
Michael Blank
5
Chloé Dambrune
3, 2
James Stunden
6
Marc Beyer
7
Joachim Schultze
7
Eicke Latz
6
Frederic Duconge
2, 3
Michael Kubbutat
4
Gunter Mayer
8, 1
3
LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
CNRS - Centre National de la Recherche Scientifique : UMR 9199, MIRCEN - Service MIRCEN : DRF/JACOB
Laia Civit 1
Author
Ioanna Theodorou 2, 3
Author IdHAL : ioanna-theodorou ORCID : https://orcid.org/0000-0001-8591-0924
Franziska Frey 1
Author
Holger Weber 4
Author
Frederic Duconge 2, 3
Author IdHAL : frederic-duconge ORCID : https://orcid.org/0000-0002-8595-0050
Michael H. G. Kubbutat 4
Author
Gunter Mayer 8, 1
Author
1
University of Bonn (D-53012 Bonn - Germany)
2
MIRCEN - Service MIRCEN (Molecular Imaging Research Center (Fontenay-aux-Roses) - France)
- JACOB - Institut de Biologie François JACOB : DRF/JACOB/MIRCEN (DRF
CEA
Fontenay-aux-Roses - France)
- DRF (CEA) - Direction de Recherche Fondamentale (CEA) : DRF/JACOB (Direction de Recherche Fondamentale
Fundamental Research Division
CEA Saclay
91191 Gif-sur-Yvette
- France)
- CEA - Commissariat à l'énergie atomique et aux énergies alternatives (Centre de Saclay Centre de Grenoble Centre de Cadarache etc - France)
- DRF (CEA) - Direction de Recherche Fondamentale (CEA) : DRF/JACOB (Direction de Recherche Fondamentale
Fundamental Research Division
CEA Saclay
91191 Gif-sur-Yvette
- France)
- Université Paris-Saclay (Bâtiment Bréguet, 3 Rue Joliot Curie 2e ét, 91190 Gif-sur-Yvette - France)
3
LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199 (18 Route du panorama CEA Fontenay-aux-Roses Bâtiment 61 92 265 Fontenay-aux-Roses CEDEX Tel : 00 33 (0)1 46 54 84 11 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR 9199 (France)
- MIRCEN - Service MIRCEN : DRF/JACOB (Molecular Imaging Research Center (Fontenay-aux-Roses) - France)
- JACOB - Institut de Biologie François JACOB : DRF/JACOB/MIRCEN (DRF
CEA
Fontenay-aux-Roses - France)
- DRF (CEA) - Direction de Recherche Fondamentale (CEA) : DRF/JACOB (Direction de Recherche Fondamentale
Fundamental Research Division
CEA Saclay
91191 Gif-sur-Yvette
- France)
- CEA - Commissariat à l'énergie atomique et aux énergies alternatives (Centre de Saclay Centre de Grenoble Centre de Cadarache etc - France)
- DRF (CEA) - Direction de Recherche Fondamentale (CEA) : DRF/JACOB (Direction de Recherche Fondamentale
Fundamental Research Division
CEA Saclay
91191 Gif-sur-Yvette
- France)
- Université Paris-Saclay (Bâtiment Bréguet, 3 Rue Joliot Curie 2e ét, 91190 Gif-sur-Yvette - France)
- JACOB - Institut de Biologie François JACOB : DRF/JACOB/MIRCEN (DRF
CEA
Fontenay-aux-Roses - France)
4
KTB - KTB Tumorforschungsgesellschaft mbH ( Research Division ProQinase, Breisacher Str. 117, 79106, Freiburg, Germany - Germany)
5
AptaIT GmbH, Am Klopferspitz (19a, 82152, Planegg, Martinsried, Germany - Germany)
6
Institute of Innate Immunity, Bonn (University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany - )
7
Life and Medical Sciences Institute for Genomics and Immunoregulation (Germany)
- University of Bonn (D-53012 Bonn - Germany)
8
Life and Medical Sciences Institute for Chemical Biology (Germany)
- University of Bonn (D-53012 Bonn - Germany)
Abstract : The targeting of specific tissue is a major challenge for the effective use of therapeutics and agents mediating this targeting are strongly demanded. We report here on an $in\ vivo$ selection technology that enables the $de\ novo$ identification of pegylated DNA aptamers pursuing tissue sites harbouring a hormone refractory prostate tumour. To this end, two libraries, one of which bearing an 11 kDa polyethylene glycol (PEG) modification, were used in an orthotopic xenograft prostate tumour mouse model for the selection process. Next-generation sequencing revealed an $in\ vivo$ enriched pegylated but not a naïve DNA aptamer recognising prostate cancer tissue implanted either subcutaneous or orthotopically in mice. This aptamer represents a valuable and cost-effective tool for the development of targeted therapies for prostate cancer. The described selection strategy and its analysis is not limited to prostate cancer but will be adaptable to various tissues, tumours, and metastases. This opens the path towards DNA aptamers being experimentally and clinically engaged as molecules for developing targeted therapy strategies.
Document type :
Journal articles
Domain :
Complete list of metadata
https://hal-cea.archives-ouvertes.fr/cea-02076516
Contributor : Frédéric Ducongé Connect in order to contact the contributor
Submitted on : Friday, March 22, 2019 - 10:51:03 AM
Last modification on : Tuesday, January 4, 2022 - 6:06:12 AM
Contributor : Frédéric Ducongé Connect in order to contact the contributor
Submitted on : Friday, March 22, 2019 - 10:51:03 AM
Last modification on : Tuesday, January 4, 2022 - 6:06:12 AM
Identifiers
- HAL Id : cea-02076516, version 1
- DOI : 10.1038/s41598-019-41460-2
Citation
Laia Civit, Ioanna Theodorou, Franziska Frey, Holger Weber, Andreas Lingnau, et al.. Targeting hormone refractory prostate cancer by $in\ vivo$ selected DNA libraries in an orthotopic xenograft mouse model. Scientific Reports, Nature Publishing Group, 2019, 9 (1), pp.4976. ⟨10.1038/s41598-019-41460-2⟩. ⟨cea-02076516⟩
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