Endothelial Retargeting of AAV9 In Vivo.

Autor: Bozoglu T; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Lee S; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Ziegler T; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Jurisch V; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Maas S; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.; Institute for Cardiovascular Prevention, Ludwigs-Maximilians-University, Munich, Germany., Baehr A; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Hinkel R; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.; Deutsches Primatenzentrum GmbH, Leibnitz-Institut für Primatenforschung, Department of Laboratory Animal Science, Göttingen, Germany., Hoenig A; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Hariharan A; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Kim CI; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Decker S; Faculty of Life Sciences, Department of Pharmaceutical Sciences, Laboratory of MacroMolecular Cancer Therapeutics (MMCT), University of Vienna, Althanstrasse 14, Vienna, 1090, Austria., Sami H; Faculty of Life Sciences, Department of Pharmaceutical Sciences, Laboratory of MacroMolecular Cancer Therapeutics (MMCT), University of Vienna, Althanstrasse 14, Vienna, 1090, Austria., Koppara T; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Oellinger R; Institute of Molecular Oncology and Functional Genomics, University Clinic rechts der Isar, Technical University of Munic, Germany., Müller OJ; Klinik für Innere Medizin III and DZHK (German Center for Cardiovascular Research), partner site Hamburg, Kiel, Lübeck., UKSH, Kiel, Germany., Frank D; Klinik für Innere Medizin III and DZHK (German Center for Cardiovascular Research), partner site Hamburg, Kiel, Lübeck., UKSH, Kiel, Germany., Megens R; Institute for Cardiovascular Prevention, Ludwigs-Maximilians-University, Munich, Germany., Nelson P; Medizinische Klinik und Poliklinik IV, Poliklinik Innenstadt, Ludwigs-Maximilians-University, Munich, Germany., Weber C; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.; Institute for Cardiovascular Prevention, Ludwigs-Maximilians-University, Munich, Germany., Schnieke A; Department of Animal Sciences, Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technical University Munich, Germany., Sperandio M; Walter Brendel Centre of Experimental Medicine and Institute of Cardiovascular Physiology and Pathophysiology, BioMedical Centre, Ludwig Maximilians University of Munich, Germany., Santamaria G; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Rad R; Institute of Molecular Oncology and Functional Genomics, University Clinic rechts der Isar, Technical University of Munic, Germany., Moretti A; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Laugwitz KL; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Soehnlein O; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.; Institute for Cardiovascular Prevention, Ludwigs-Maximilians-University, Munich, Germany.; Institute for Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), WWU Münster, Germany., Ogris M; Faculty of Life Sciences, Department of Pharmaceutical Sciences, Laboratory of MacroMolecular Cancer Therapeutics (MMCT), University of Vienna, Althanstrasse 14, Vienna, 1090, Austria., Kupatt C; Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University Munich, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2022 Mar; Vol. 9 (7), pp. e2103867. Date of Electronic Publication: 2022 Jan 12.
DOI: 10.1002/advs.202103867
Abstrakt: Adeno-associated viruses (AAVs) are frequently used for gene transfer and gene editing in vivo, except for endothelial cells, which are remarkably resistant to unmodified AAV-transduction. AAVs are retargeted here toward endothelial cells by coating with second-generation polyamidoamine dendrimers (G2) linked to endothelial-affine peptides (CNN). G2 CNN AAV9-Cre (encoding Cre recombinase) are injected into mTmG-mice or mTmG-pigs, cell-specifically converting red to green fluorescence upon Cre-activity. Three endothelial-specific functions are assessed: in vivo quantification of adherent leukocytes after systemic injection of - G2 CNN AAV9 encoding 1) an artificial adhesion molecule (S1FG) in wildtype mice (day 10) or 2) anti-inflammatory Annexin A1 (Anxa1) in ApoE -/- mice (day 28). Moreover, 3) in Cas9-transgenic mice, blood pressure is monitored till day 56 after systemic application of G2 CNN AAV9-gRNAs, targeting exons 6-10 of endothelial nitric oxide synthase (eNOS), a vasodilatory enzyme. G2 CNN AAV9-Cre transduces microvascular endothelial cells in mTmG-mice or mTmG-pigs. Functionally, G2 CNN AAV9-S1FG mediates S1FG-leukocyte adhesion, whereas G2 CNN AAV9-Anxa1-application reduces long-term leukocyte recruitment. Moreover, blood pressure increases in Cas9-expressing mice subjected to G2 CNN AAV9-gRNA eNOS . Therefore, G2 CNN AAV9 may enable gene transfer in vascular and atherosclerosis models.
(© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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