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Table 1. The strengths and weaknesses of adenovirus vectors for revascularisation therapy
Very high efficiency^ allows the use of low viral doses Production of high-titer viral lots
Transduction of proliferating and quiescent cells Extra-chromosomal retentions safety Several serotypes known Relatively high transgene capacity
Transient expression (1st and 2nd generation vectors) Repeated administration impossible with the same serotype Immune responses
Limited tropism for skeletal muscle deleted viruses) up to 30kbp (high capacity gutless vectors with E1, E2, E3 and E4 deletions). AdVs can be produced in high titers (1012-1013viral particles/ml), which makes them feasible also in clinical use. Revascularisation therapies of ischemic tissues with AdVs (most commonly serotypes Ad2 and Ad5) encoding angiogenic growth factors, such as members of the vascular endothelial growth factor (VEGF) family remain an intriguing option for patients who cannot be treated with conventional therapies . Pre-clinical studies with AdVs encoding various VEGFs in rabbit skeletal muscle have shown that several-fold increases in muscle perfusion can be achieved [3, 4]. This evidence supports the concept of AdV being the most effective gene therapy vector currently in use, with enormous potential for both basic research and clinical gene therapy. The strengths and weaknesses of AdVs for gene therapy are summarised in Table 1 and further discussed in the following paragraphs.
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