Article

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

Division of Human Gene Therapy, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Virology (impact factor: 3.35). 11/2010; 407(2):196-205. DOI:10.1016/j.virol.2010.08.010
Source: PubMed

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.

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Keywords

adenovirus receptor
 
adenovirus receptors
 
aggressive tumor cells
 
CAR expression decreases
 
cellular receptor
 
chimeric HAdV-3 fiber
 
different expression levels
 
extensive transduction
 
fiber-mosaic HAdV vector
 
fiber-mosaic HAdV vectors
 
HAdV receptors
 
HAdV-5 fiber protein
 
HAdV-5-based vectors
 
heterogeneous cell population
 
heterogeneous population
 
mosaic HAdV vector
 
primary receptor
 
structural integrity
 
tumors progress
 
varying expression levels