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Targeting hormone refractory prostate cancer by in vivo selected DNA libraries in an orthotopic xenograft mouse model

Authors
  • Civit, Laia1
  • Theodorou, Ioanna2
  • Frey, Franziska1
  • Weber, Holger3, 4
  • Lingnau, Andreas3, 5
  • Gröber, Carsten6
  • Blank, Michael6
  • Dambrune, Chloé2
  • Stunden, James7
  • Beyer, Marc8, 9, 10
  • Schultze, Joachim8, 9
  • Latz, Eicke7
  • Ducongé, Frédéric2
  • Kubbutat, Michael H. G.3, 4
  • Mayer, Günter1, 11
  • 1 University of Bonn, Gerhard-Domagk-Str. 1, Chemical Biology and Chemical Genetics, Life and Medical Sciences (LIMES) Institute, Bonn, 53121, Germany , Bonn (Germany)
  • 2 UMR CNRS 9199, 18 Route du Panorama, CEA, DRT, Institut de biologie François-Jacob, Molecular Imaging Research Center (MIRCen), Roses, 92260, France , Roses (France)
  • 3 Research Division ProQinase, KTB Tumorforschungsgesellschaft mbH, Breisacher Str. 117, Freiburg, 79106, Germany , Freiburg (Germany)
  • 4 ProQinase GmbH, Breisacher Straße 117, Freiburg, 79106, Germany , Freiburg (Germany)
  • 5 Genmab B.V., Yalelaan 60, Utrecht, 3584 CM, The Netherlands , Utrecht (Netherlands)
  • 6 AptaIT GmbH, Am Klopferspitz 19a, Planegg, Martinsried, 82152, Germany , Planegg (Germany)
  • 7 University Hospital Bonn, Institute of Innate Immunity, Sigmund-Freud-Str. 25, Bonn, 53127, Germany , Bonn (Germany)
  • 8 University of Bonn, Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, Carl-Troll-Straße 31, Bonn, 53115, Germany , Bonn (Germany)
  • 9 Platform for Single Cell Genomics and Epigenomics at the DZNE and the University of Bonn, Sigmund-Freud-Str. 27, Bonn, 53127, Germany , Bonn (Germany)
  • 10 German Center for Neurodegenerative Diseases (DZNE), Molecular Immunology in Neurodegeneration, Sigmund-Freud-Str. 27, Bonn, 53127, Germany , Bonn (Germany)
  • 11 University of Bonn, Center of Aptamer Research and Development (CARD), Gerhard-Domagk Str. 1, Bonn, 53121, Germany , Bonn (Germany)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Mar 21, 2019
Volume
9
Issue
1
Identifiers
DOI: 10.1038/s41598-019-41460-2
Source
Springer Nature
License
Green

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.

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