Universität zu Köln

Buening, Hildegard, Huber, Anke, Zhang, Liang, Meumann, Nadja and Hacker, Ulrich ORCID: 0000-0002-3253-8206 (2015). Engineering the AAV capsid to optimize vector-host-interactions. Curr. Opin. Pharmacol., 24. S. 94 - 105. OXFORD: ELSEVIER SCI LTD. ISSN 1471-4973

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Abstract

Adeno-associated viral (AAV) vectors are the most widely used delivery system for in vivo gene therapy. Vectors developed from natural AAV isolates achieved clinical benefit for a number of patients suffering from monogenetic disorders. However, high vector doses were required and the presence of preexisting neutralizing antibodies precluded a number of patients from participation. Further challenges are related to AAV's tropism that lacks cell type selectivity resulting in off-target transduction. Conversely, specific cell types representing important targets for gene therapy like stem cells or endothelial cells show low permissiveness. To overcome these limitations, elegant rational design- as well as directed evolution-based strategies were developed to optimize various steps of AAV's host interaction. These efforts resulted in next generation vectors with enhanced capabilities, that is increased efficiency of cell transduction, targeted transduction of previously non-permissive cell types, escape from antibody neutralization and off-target free in vivo delivery of vector genomes. These important achievements are expected to improve current and pave the way towards novel AAV-based applications in gene therapy and regenerative medicine.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Buening, Hildegard UNSPECIFIED UNSPECIFIED UNSPECIFIED Huber, Anke UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Liang UNSPECIFIED UNSPECIFIED UNSPECIFIED Meumann, Nadja UNSPECIFIED UNSPECIFIED UNSPECIFIED Hacker, Ulrich UNSPECIFIED orcid.org/0000-0002-3253-8206 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-391941
DOI:	10.1016/j.coph.2015.08.002
Journal or Publication Title:	Curr. Opin. Pharmacol.
Volume:	24
Page Range:	S. 94 - 105
Date:	2015
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1471-4973
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ADENOASSOCIATED VIRUS TYPE-2; HEPARAN-SULFATE PROTEOGLYCAN; SITE-SPECIFIC MODIFICATION; ENHANCED GENE DELIVERY; DIRECTED EVOLUTION; VIRAL-VECTORS; IN-VITRO; TRANSDUCTION EFFICIENCY; THERAPY VECTOR; PROTEIN Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39194