Koerbelin, Jakob, Dogbevia, Godwin, Michelfelder, Stefan, Ridder, Dirk A., Hunger, Agnes, Wenzel, Jan, Seismann, Henning, Lampe, Melanie, Bannach, Jacqueline, Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Kleinschmidt, Juergen A., Schwaninger, Markus and Trepel, Martin (2016). A brain microvasculature endothelial cell-specific viral vector with the potential to treat neurovascular and neurological diseases. EMBO Mol. Med., 8 (6). S. 609 - 626. HOBOKEN: WILEY-BLACKWELL. ISSN 1757-4684

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Abstract

Gene therapy critically relies on vectors that combine high transduction efficiency with a high degree of target specificity and that can be administered through a safe intravenous route. The lack of suitable vectors, especially for gene therapy of brain disorders, represents a major obstacle. Therefore, we applied an invivo screening system of random ligand libraries displayed on adeno-associated viral capsids to select brain-targeted vectors for the treatment of neurovascular diseases. We identified a capsid variant showing an unprecedented degree of specificity and long-lasting transduction efficiency for brain microvasculature endothelial cells as the primary target of selection. A therapeutic vector based on this selected viral capsid was used to markedly attenuate the severe cerebrovascular pathology of mice with incontinentia pigmenti after a single intravenous injection. Furthermore, the versatility of this selection system will make it possible to select ligands for additional invivo targets without requiring previous identification of potential target-specific receptors.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koerbelin, JakobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dogbevia, GodwinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michelfelder, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ridder, Dirk A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunger, AgnesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wenzel, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seismann, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lampe, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bannach, JacquelineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
Kleinschmidt, Juergen A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwaninger, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trepel, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-274395
DOI: 10.15252/emmm.201506078
Journal or Publication Title: EMBO Mol. Med.
Volume: 8
Number: 6
Page Range: S. 609 - 626
Date: 2016
Publisher: WILEY-BLACKWELL
Place of Publication: HOBOKEN
ISSN: 1757-4684
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ADENOASSOCIATED VIRUS VECTORS; DISPLAY PEPTIDE LIBRARIES; TARGETED GENE DELIVERY; IN-VIVO; AAV VECTOR; INCONTINENTIA PIGMENTI; DIRECTED EVOLUTION; ADULT BRAIN; MOUSE MODEL; TRANSDUCTIONMultiple languages
Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27439

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