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

Academic Article

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. © 2010.
  • Authors

    Published In

  • Virology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Murakami M; Ugai H; Wang M; Belousova N; Dent P; Fisher PB; Glasgow JN; Everts M; Curiel DT
  • Start Page

  • 196
  • End Page

  • 205
  • Volume

  • 407
  • Issue

  • 2