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Endothelial Retargeting of AAV9 In Vivo

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 (...

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Autores principales: Bozoglu, Tarik, Lee, Seungmin, Ziegler, Tilman, Jurisch, Victoria, Maas, Sanne, Baehr, Andrea, Hinkel, Rabea, Hoenig, Amelie, Hariharan, Anjana, Kim, Christina Inyeop, Decker, Simon, Sami, Haider, Koppara, Tobias, Oellinger, Ruppert, Müller, Oliver J., Frank, Derk, Megens, Remco, Nelson, Peter, Weber, Christian, Schnieke, Angelika, Sperandio, Markus, Santamaria, Gianluca, Rad, Roland, Moretti, Alessandra, Laugwitz, Karl‐Ludwig, Soehnlein, Oliver, Ogris, Manfred, Kupatt, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895123/
https://www.ncbi.nlm.nih.gov/pubmed/35023328
http://dx.doi.org/10.1002/advs.202103867
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author Bozoglu, Tarik
Lee, Seungmin
Ziegler, Tilman
Jurisch, Victoria
Maas, Sanne
Baehr, Andrea
Hinkel, Rabea
Hoenig, Amelie
Hariharan, Anjana
Kim, Christina Inyeop
Decker, Simon
Sami, Haider
Koppara, Tobias
Oellinger, Ruppert
Müller, Oliver J.
Frank, Derk
Megens, Remco
Nelson, Peter
Weber, Christian
Schnieke, Angelika
Sperandio, Markus
Santamaria, Gianluca
Rad, Roland
Moretti, Alessandra
Laugwitz, Karl‐Ludwig
Soehnlein, Oliver
Ogris, Manfred
Kupatt, Christian
author_facet Bozoglu, Tarik
Lee, Seungmin
Ziegler, Tilman
Jurisch, Victoria
Maas, Sanne
Baehr, Andrea
Hinkel, Rabea
Hoenig, Amelie
Hariharan, Anjana
Kim, Christina Inyeop
Decker, Simon
Sami, Haider
Koppara, Tobias
Oellinger, Ruppert
Müller, Oliver J.
Frank, Derk
Megens, Remco
Nelson, Peter
Weber, Christian
Schnieke, Angelika
Sperandio, Markus
Santamaria, Gianluca
Rad, Roland
Moretti, Alessandra
Laugwitz, Karl‐Ludwig
Soehnlein, Oliver
Ogris, Manfred
Kupatt, Christian
author_sort Bozoglu, Tarik
collection PubMed
description 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.
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spelling pubmed-88951232022-03-10 Endothelial Retargeting of AAV9 In Vivo Bozoglu, Tarik Lee, Seungmin Ziegler, Tilman Jurisch, Victoria Maas, Sanne Baehr, Andrea Hinkel, Rabea Hoenig, Amelie Hariharan, Anjana Kim, Christina Inyeop Decker, Simon Sami, Haider Koppara, Tobias Oellinger, Ruppert Müller, Oliver J. Frank, Derk Megens, Remco Nelson, Peter Weber, Christian Schnieke, Angelika Sperandio, Markus Santamaria, Gianluca Rad, Roland Moretti, Alessandra Laugwitz, Karl‐Ludwig Soehnlein, Oliver Ogris, Manfred Kupatt, Christian Adv Sci (Weinh) Research Articles 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. John Wiley and Sons Inc. 2022-01-12 /pmc/articles/PMC8895123/ /pubmed/35023328 http://dx.doi.org/10.1002/advs.202103867 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Bozoglu, Tarik
Lee, Seungmin
Ziegler, Tilman
Jurisch, Victoria
Maas, Sanne
Baehr, Andrea
Hinkel, Rabea
Hoenig, Amelie
Hariharan, Anjana
Kim, Christina Inyeop
Decker, Simon
Sami, Haider
Koppara, Tobias
Oellinger, Ruppert
Müller, Oliver J.
Frank, Derk
Megens, Remco
Nelson, Peter
Weber, Christian
Schnieke, Angelika
Sperandio, Markus
Santamaria, Gianluca
Rad, Roland
Moretti, Alessandra
Laugwitz, Karl‐Ludwig
Soehnlein, Oliver
Ogris, Manfred
Kupatt, Christian
Endothelial Retargeting of AAV9 In Vivo
title Endothelial Retargeting of AAV9 In Vivo
title_full Endothelial Retargeting of AAV9 In Vivo
title_fullStr Endothelial Retargeting of AAV9 In Vivo
title_full_unstemmed Endothelial Retargeting of AAV9 In Vivo
title_short Endothelial Retargeting of AAV9 In Vivo
title_sort endothelial retargeting of aav9 in vivo
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895123/
https://www.ncbi.nlm.nih.gov/pubmed/35023328
http://dx.doi.org/10.1002/advs.202103867
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