Universität zu Köln

Maersch, Stephan, Huber, Anke, Hallek, Michael, Buening, Hildegard and Perabo, Luca (2010). A Novel Directed Evolution Method to Enhance Cell-Type Specificity of Adeno-Associated Virus Vectors. Comb. Chem. High Throughput Screen, 13 (9). S. 807 - 813. SHARJAH: BENTHAM SCIENCE PUBL LTD. ISSN 1875-5402

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Abstract

Clinical application of viral vectors is often hampered by the lack of selectivity of viral particles for the targeted tissue. This drawback decreases the efficiency of gene delivery and raises safety concerns. We successfully established a novel in vitro evolution protocol to engineer adeno-associated virus vectors with increased selectivity for designated target cells. Subjecting a peptide-display library of AAV capsids to negative selection cycles on human primary fibroblasts and to positive selection cycles on a human melanoma cell line, we isolated several variants with up to 3.7-fold increased specificity for malignant cells in comparison to fibroblasts and other cell types. These mutants can be used to achieve high levels of gene transfer to target cells reducing undesired transduction of neighbouring tissues.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Maersch, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Huber, Anke UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Buening, Hildegard UNSPECIFIED UNSPECIFIED UNSPECIFIED Perabo, Luca UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-493105
DOI:	10.2174/138620710792927385
Journal or Publication Title:	Comb. Chem. High Throughput Screen
Volume:	13
Number:	9
Page Range:	S. 807 - 813
Date:	2010
Publisher:	BENTHAM SCIENCE PUBL LTD
Place of Publication:	SHARJAH
ISSN:	1875-5402
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VIRAL VECTORS; IN-VITRO; GENE; TROPISM; AAV; LIBRARIES; SELECTION; DISPLAY Multiple languages Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49310