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

Laia Civit; Ioanna Theodorou; Franziska Frey; Holger Weber; Andreas Lingnau; Carsten Gröber; Michael Blank; Chloé Dambrune; James Stunden; Marc Beyer; Joachim Schultze; Eicke Latz; Frederic Duconge; Michael Kubbutat; Gunter Mayer

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}

1 University of Bonn

2 MIRCEN - Service MIRCEN

3 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199

UP11 - Université Paris-Sud - Paris 11, MIRCEN - Service MIRCEN : DRF/JACOB, CNRS - Centre National de la Recherche Scientifique : UMR 9199

4 KTB - KTB Tumorforschungsgesellschaft mbH

5 AptaIT GmbH, Am Klopferspitz

6 Institute of Innate Immunity, Bonn

7 Life and Medical Sciences Institute for Genomics and Immunoregulation

8 Life and Medical Sciences Institute for Chemical Biology

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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Journal articles

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Life Sciences [q-bio]

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https://hal-cea.archives-ouvertes.fr/cea-02076516
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Submitted on : Friday, March 22, 2019 - 10:51:03 AM
Last modification on : Thursday, May 9, 2019 - 11:54:01 AM

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

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

Annex

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