In vitro and in vivo properties of adenovirus vectors with increased affinity to CD46

Hongjie Wang, Ying Liu, Zong Yi Li, Sebastian Tuve, Daniel Stone, Oleksandr Kalyushniy, Dmitry Shayakhmetov, Christophe L.M. Verlinde, Thilo Stehle, John McVey, Andrew Baker, Kah Whye Peng, Steve Roffler, André Lieber

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Gene transfer vectors containing adenovirus (Ad) serotype 35 (Ad35) fibers have shown promise for cancer and stem cell gene therapy. In this study, we attempted to improve the in vitro and in vivo infection properties of these vectors by increasing their affinity to the Ad35 fiber receptor CD46. We constructed Ad vectors containing either the wild-type Ad35 fiber knob (Ad5/35) or Ad35 knob mutants with 4-fold- and 60-fold-higher affinity to CD46 (Ad5/35+ and Ad5/35++, respectively). In in vitro studies with cell lines, the higher affinities of Ad5/35+ and Ad5/35++ to CD46 did not translate into correspondingly higher transduction efficiencies, regardless of the CD46 receptor density present on cells. However, in vivo, in a mouse model with preestablished CD46high liver metastases, intravenous injection of Ad5/35++ resulted in more-efficient tumor cell transduction. We conclude that Ad5/35 vectors with increased affinity to CD46 have an advantage in competing with non-CD46-mediated sequestration of vector particles after intravenous injection.

Original languageEnglish (US)
Pages (from-to)10567-10579
Number of pages13
JournalJournal of virology
Volume82
Issue number21
DOIs
StatePublished - Nov 2008

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Wang, H., Liu, Y., Li, Z. Y., Tuve, S., Stone, D., Kalyushniy, O., Shayakhmetov, D., Verlinde, C. L. M., Stehle, T., McVey, J., Baker, A., Peng, K. W., Roffler, S., & Lieber, A. (2008). In vitro and in vivo properties of adenovirus vectors with increased affinity to CD46. Journal of virology, 82(21), 10567-10579. https://doi.org/10.1128/JVI.01308-08