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

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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
Creators:
CreatorsEmailORCIDORCID Put Code
Muench, Robert C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muth, AnkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muik, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedel, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmatz, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dreier, BirgitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trkola, AlexandraUNSPECIFIEDorcid.org/0000-0003-1013-876XUNSPECIFIED
Plueckthun, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buening, HildegardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buchholz, Christian J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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
Uncontrolled Keywords:
KeywordsLanguage
SULFATE PROTEOGLYCAN BINDING; ADENOASSOCIATED VIRUS TYPE-2; RIBOSOME DISPLAY; AAV VECTORS; THERAPY; CELLS; LIBRARIES; DARPINS; TROPISM; PEPTIDEMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41409

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