Capsid Engineering Overcomes Barriers Toward Adeno-Associated Virus Vector-Mediated Transduction of Endothelial Cells

L Zhang, A Rossi, L Lange, N Meumann, U Koitzsch, Kathleen Christie, M. Andrew Nesbit, Tara C. B. Moore, U.T. Hacker, M. Morgan, D. Hoffmann, James Zengel, Jan E. Carette, A. Schambach, A. Salvetti, Margarete Odenthal, Hildegard Büning

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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.

Original languageEnglish
Pages (from-to)1284-1296
Number of pages13
JournalHuman Gene Therapy
Issue number10
Early online date13 Aug 2019
Publication statusPublished (in print/issue) - 23 Sept 2019

Bibliographical note

Funding Information:
This work was supported by grants from University Hospital Cologne (Kln Fortune) to H.B. and M.O., the Center for Molecular Medicine Cologne (CMMC) to H.B., BMBF and MWK Lower Saxony-funded Professorinnenprogramm Niedersachsen to H.B., the DFG-funded KFO286 to H.B., the DFG-funded cluster of excellence REBIRTH EXC62/2 to A.S. and H.B., and the DFG-funded SFB738 to A.S. L.Z. held a scholarship from the German Academic Exchange Service (DAAD).

Publisher Copyright:
© 2019, Mary Ann Liebert, Inc.

Copyright 2019 Elsevier B.V., All rights reserved.


  • AAV vectors
  • endothelial cells
  • induced pluripotent stem cells
  • uncoating
  • uptake


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