An adenoviral vector expressing human adenovirus 5 and 3 fiber proteins for targeting heterogeneous cell populations

Miho Murakami, Hideyo Ugai, Minghui Wang, Natalya Belousova, Paul Dent, Paul B. Fisher, Joel N. Glasgow, Maaike Everts, David T. Curiel

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Human adenovirus serotype 5 (HAdV-5) attaches to its primary receptor, the coxsackie and adenovirus receptor (CAR) as the first step of infection. However, CAR expression decreases as tumors progress, thereby diminishing the utility of HAdV-5-based vectors for cancer therapy. In contrast, many aggressive tumor cells highly express CD46, a cellular receptor for HAdV-3. We hypothesized that a mosaic HAdV vector, containing two kinds of fiber proteins, would provide extensive transduction in a heterogeneous population of tumor cells with varying expression levels of HAdV receptors. We therefore generated a fiber-mosaic HAdV vector displaying both a chimeric HAdV-3 fiber and the HAdV-5 fiber protein. We verified the structural integrity of purified viral particles and confirmed that the fiber-mosaic HAdV vector has expanded tropism. We conclude that the use of fiber-mosaic HAdV vectors is a promising approach for transducing a heterogeneous cell population with different expression levels of adenovirus receptors.

Original languageEnglish
Pages (from-to)196-205
Number of pages10
JournalVirology
Volume407
Issue number2
DOIs
StatePublished - Nov 25 2010
Externally publishedYes

Keywords

  • Adenovirus
  • Fiber
  • Mosaic
  • Tropism expansion
  • Tumor

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    Murakami, M., Ugai, H., Wang, M., Belousova, N., Dent, P., Fisher, P. B., Glasgow, J. N., Everts, M., & Curiel, D. T. (2010). An adenoviral vector expressing human adenovirus 5 and 3 fiber proteins for targeting heterogeneous cell populations. Virology, 407(2), 196-205. https://doi.org/10.1016/j.virol.2010.08.010