Universität zu Köln

Zhang, L., Rossi, A., Lange, L., Meumann, N., Koitzsch, U., Christie, K., Nesbit, M. A., Moore, C. B. T., Hacker, U. T., Morgan, M., Hoffmann, D., Zengel, J., Carette, J. E., Schambach, A., Salvetti, A., Odenthal, M. and Buening, H. (2019). Capsid Engineering Overcomes Barriers Toward Adeno-Associated Virus Vector-Mediated Transduction of Endothelial Cells. Hum. Gene Ther., 30 (10). S. 1284 - 1297. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 1557-7422

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Abstract

Endothelial cells (EC) are targets in gene therapy and regenerative medicine, but they are inefficiently transduced with adeno-associated virus (AAV) vectors of various serotypes. To identify barriers hampering efficient transduction and to develop an optimized AAV variant for EC transduction, we screened an AAV serotype 2-based peptide display library on primary human macrovascular EC. Using a new high-throughput selection and monitoring protocol, we identified a capsid variant, AAV-V-EC, which outperformed the parental serotype as well as first-generation targeting vectors in EC transduction. AAV vector uptake was improved, resulting in significantly higher transgene expression levels from single-stranded vector genomes detectable within a few hours post-transduction. Notably, AAV-V-EC transduced not only proliferating EC but also quiescent EC, although higher particle-per-cell ratios had to be applied. Also, induced pluripotent stem cell-derived endothelial progenitor cells, a novel tool in regenerative medicine and gene therapy, were highly susceptible toward AAV-V-EC transduction. Thus, overcoming barriers by capsid engineering significantly expands the AAV tool kit for a wide range of applications targeting EC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zhang, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rossi, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lange, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Meumann, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koitzsch, U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Christie, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nesbit, M. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moore, C. B. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hacker, U. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Morgan, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zengel, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Carette, J. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schambach, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Salvetti, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buening, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-132844
DOI:	10.1089/hum.2019.027
Journal or Publication Title:	Hum. Gene Ther.
Volume:	30
Number:	10
Page Range:	S. 1284 - 1297
Date:	2019
Publisher:	MARY ANN LIEBERT, INC
Place of Publication:	NEW ROCHELLE
ISSN:	1557-7422
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEPARAN-SULFATE PROTEOGLYCAN; PLURIPOTENT STEM-CELLS; TARGETED GENE DELIVERY; PROGENITOR CELLS; IN-VIVO; VIRAL VECTORS; AAV VECTORS; THERAPY; TROPISM; EFFICIENT Multiple languages Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13284