Journal
VIRUSES-BASEL
Volume 2, Issue 9, Pages 2134-2153Publisher
MDPI AG
DOI: 10.3390/v2092134
Keywords
canine adenovirus; vectors; CAV-2; CAR; gene therapy; neurons; immunity; retrograde transport; neurodegenerative diseases; vaccines
Categories
Funding
- Agence Nationale pour la recherche
- European Community
- Fondation de France
- Region Languedoc Roussillon
- Association Francaise contre les Myopathies
- Vaincre les Maladies Lysosomales
- Association pour la Recherche sur la Sclerose Lateral Amytrophique et autres maladies du motoneurone
- Motor Neuron Disease Association (MNDA)
- European Research Projects on Rare Diseases
- Foundation Beatriu de Pinos
- Cystinosis Research Foundation
- Cystinosis Research Network
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Adenovirus vectors have significant potential for long- or short-term gene transfer. Preclinical and clinical studies using human derived adenoviruses (HAd) have demonstrated the feasibility of flexible hybrid vector designs, robust expression and induction of protective immunity. However, clinical use of HAd vectors can, under some conditions, be limited by pre-existing vector immunity. Pre-existing humoral and cellular anti-capsid immunity limits the efficacy and duration of transgene expression and is poorly circumvented by injections of larger doses and immuno-suppressing drugs. This review updates canine adenovirus serotype 2 (CAV-2, also known as CAdV-2) biology and gives an overview of the generation of early region 1 (E1)-deleted to helper-dependent (HD) CAV-2 vectors. We also summarize the essential characteristics concerning their interaction with the anti-HAd memory immune responses in humans, the preferential transduction of neurons, and its high level of retrograde axonal transport in the central and peripheral nervous system. CAV-2 vectors are particularly interesting tools to study the pathophysiology and potential treatment of neurodegenerative diseases, as anti-tumoral and anti-viral vaccines, tracer of synaptic junctions, oncolytic virus and as a platform to generate chimeric vectors.
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