Muench, Robert C., Muth, Anke, Muik, Alexander, Friedel, Thorsten, Schmatz, Julia, Dreier, Birgit, Trkola, Alexandra ORCID: 0000-0003-1013-876X, Plueckthun, Andreas, Buening, Hildegard and Buchholz, Christian J. (2015). Off-target-free gene delivery by affinity-purified receptor-targeted viral vectors. Nat. Commun., 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723
Full text not available from this repository.Abstract
We describe receptor-targeted adeno-associated viral (AAV) vectors that allow genetic modification of rare cell types ex vivo and in vivo while showing no detectable off-targeting. Displaying designed ankyrin repeat proteins (DARPins) on the viral capsid and carefully depleting DARPin-deficient particles, AAV vectors were made specific for Her2/neu, EpCAM or CD4. A single intravenous administration of vector targeted to the tumour antigen Her2/neu was sufficient to track 75% of all tumour sites and to extend survival longer than the cytostatic antibody Herceptin. CD4-targeted AAVs hit human CD4-positive cells present in spleen of a humanized mouse model, while CD8-positive cells as well as liver or other off-target organs remained unmodified. Mimicking conditions of circulating tumour cells, EpCAM-AAV detected single tumour cells in human blood opening the avenue for tumour stem cell tracking. Thus, the approach developed here delivers genes to target cell types of choice with antibody-like specificity.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-414095 | ||||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/ncomms7246 | ||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nat. Commun. | ||||||||||||||||||||||||||||||||||||||||||||
Volume: | 6 | ||||||||||||||||||||||||||||||||||||||||||||
Date: | 2015 | ||||||||||||||||||||||||||||||||||||||||||||
Publisher: | NATURE PUBLISHING GROUP | ||||||||||||||||||||||||||||||||||||||||||||
Place of Publication: | LONDON | ||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 2041-1723 | ||||||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/41409 |
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