CAR chasing: canine adenovirus vectors–all bite and no bark?

Abstract

SummaryThis review deals primarily with canine adenovirus serotype 2 (CAV-2) vectors and gives a simplified overview of how the various domains of virology, cellular and molecular biology, as well as immunology, come into play when trying to understand and ameliorate adenovirus (Ad)-mediated gene transfer. The generation of early region 1 (E1)-deleted ( E1) CAV-2 vectors, the lack of pre-existing humoral immunity, trafficking, the use of the coxsackie B adenovirus receptor (CAR), the surprising neuronal tropism, and the ability to migrate via axons to afferent regions of the central and peripheral nervous system, are described. Due to these intrinsic properties, CAV-2 vectors may be powerful tools for the study of the pathophysiology and potential treatment of neurodegenerative diseases like lysosomal storage disorders, Parkinson's, Alzheimer's, Huntington's, amyotrophic lateral sclerosis, and others. Other potential uses include anti-tumoral and anti-viral vaccines, tracer of synaptic junctions, pain therapy, cancer therapy (e.g. K9 CRAds), and gene transfer to other somatic tissues.

A human adenoviral vector with a chimeric fiber from canine adenovirus type 1 results in novel expanded tropism for cancer gene therapy

“…14 Another canine adenovirus strain, serotype 1 (CAV-1), has also been partially characterized. Whereas, its cell entry biology has not been described to the extent that has been accomplished for CAV-2, the pathological, structural, biophysical, and serological dissimilarities of CAV1 [19][20][21][22][23][24] in comparison to CAV-2 suggest that a distinct underlying tropism may be operational. In light of these considerations, we explored the potential utilization of an adenoviral xenotype possessing the fiber-knob of CAV-1.…”

Contrasting Effects of Human, Canine, and Hybrid Adenovirus Vectors on the Phenotypical and Functional Maturation of Human Dendritic Cells: Implications for Clinical Efficacy

“…Surprisingly, Adenoviridae probably share an ancient common ancestor with bacteriophages of the Tectiviridae family (1,6,7). Several years ago we began developing vectors derived from canine adenovirus serotype 2 (CAV-2) (39,41,(71)(72)(73)(74), one of the greater than 60 nonhuman Adenoviridae. In the central nervous sys-tems (CNS) of several species, CAV-2 vectors preferentially transduce neurons and lead to an efficient level of axoplasmic transport (73).…”

Enhanced Gene Delivery to Human Primary Endothelial Cells Using Tropism-Modified Adenovirus Vectors

“…Whereas infection with Ad5Luc1-CK1 and Ad5Luc1-CK2 increased infectivity in HUVEC 100 and 200-fold respectively, the exact mechanisms of binding and internalization of these canine Ads are not yet fully characterized. Studies have shown that canine Ad 2 knob binds to CAR but the presence of recombinant Ad5 knob only partially blocks this binding [19,28]. Also, CK1 appears to display CAR-independent infection [19].…”