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

作者：Murakami Miho; Ugai Hideyo; Wang Minghui; Belousova Natalya; Dent Paul; Fisher Paul B; Glasgow Joel N; Everts Maaike; Curiel David T^*

来源：Virology, 2010, 407(2): 196-205.

DOI：10.1016/j.virol.2010.08.010

• Adenovirus
• Mosaic
• Fiber
• Tumor
• Tropism expansion

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. Published by Elsevier Inc.

• 出版日期2010-11-25