Received August 19, 2004
Revised October 15, 2004
Accepted after revision October 15, 2004
Cell-Selective Viral Gene Delivery Vectors For The Vasculature
Andrew H Baker 1*,
lorraine Work 1,
Angelika Kritz 1,
Stuart A 2
1 University of Glasgow
2 Nicklin
* To whom correspondence should be addressed. E-mail: ab11f{at}clinmed.gla.ac.uk.
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Abstract |
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Clinical gene therapy for cardiovascular disease remains achievable. To date however, pre-clinical studies and clinical trials have highlighted shortfalls in viral gene delivery to vascular cells. These include poor efficiency, poor target tissue selectivity, the presence of pre-existing neutralising antibodies and immunogenicity generated by the host to vectors such as adenovirus (Ad). These important issues require careful consideration when applying viral vectors for gene therapy. Each delivery vector requires precise optimisation and tailoring for each disease application since parameters relating to vecor:tissue exposure time, route of delivery and target cell type vary considerably. Optimisation can be achieved through modification of the structure of the virus capsid proteins and expression cassette to generate vectors that are highly selective and efficient for target cell binding and entry as well as instilling transcriptional control and/or longevity on transgene expression. This ultimately will improve the efficacy and toxicity profiles of gene delivery vectors and has become a very important area in gene therapy. Here, we review recent advances in the targeting of viral gene delivery vectors to the vasculature.
Key Words:
Endothelial cell, Endothelium, Molecular biology