Targeting hormone refractory prostate cancer by in vivo selected DNA libraries in an orthotopic xenograft mouse model
| Autor: | Ioanna Theodorou, Holger Weber, Franziska Frey, Joachim L. Schultze, Chloé Dambrune, Andreas Lingnau, Carsten Gröber, Günter Mayer, James Stunden, Michael H.G. Kubbutat, Michael Blank, Frédéric Ducongé, Laia Civit, Marc Beyer, Eicke Latz |
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| Přispěvatelé: | Universität Bonn = University of Bonn, Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), KTB Tumorforschungsgesellschaft mbH (KTB), AptaIT GmbH, Am Klopferspitz, Institute of Innate Immunity, Bonn, Life and Medical Sciences Institute for Genomics and Immunoregulation, Life and Medical Sciences Institute for Chemical Biology, University of Bonn, Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male metabolism [Aptamers Nucleotide] Aptamer medicine.medical_treatment [SDV]Life Sciences [q-bio] lcsh:Medicine Mice Nude Article Targeted therapy Polyethylene Glycols 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine In vivo Prostate Cell Line Tumor medicine Animals Humans Genomic library pathology [Prostatic Neoplasms] lcsh:Science Gene Library Multidisciplinary Base Sequence pharmacology [Potassium] business.industry lcsh:R Prostatic Neoplasms Aptamers Nucleotide medicine.disease Xenograft Model Antitumor Assays 3. Good health Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry [Polyethylene Glycols] chemistry Cell culture Cancer research Potassium lcsh:Q business ddc:600 030217 neurology & neurosurgery DNA |
| Zdroj: | Scientific reports 9(1), 4976 (2019). doi:10.1038/s41598-019-41460-2 Scientific Reports Scientific Reports, 2019, 9 (1), pp.4976. ⟨10.1038/s41598-019-41460-2⟩ Scientific Reports, Nature Publishing Group, 2019, 9 (1), pp.4976. ⟨10.1038/s41598-019-41460-2⟩ Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-41460-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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