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:
CreatorsEmailORCIDORCID Put Code
Zhang, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rossi, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lange, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meumann, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koitzsch, U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christie, K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nesbit, M. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moore, C. B. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hacker, U. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morgan, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zengel, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carette, J. E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schambach, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salvetti, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odenthal, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buening, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
HEPARAN-SULFATE PROTEOGLYCAN; PLURIPOTENT STEM-CELLS; TARGETED GENE DELIVERY; PROGENITOR CELLS; IN-VIVO; VIRAL VECTORS; AAV VECTORS; THERAPY; TROPISM; EFFICIENTMultiple languages
Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13284

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