The Strengths And Weaknesses Of Vegf Adenovirusdriven Angiogenesis

PETRA KORPISALO1, TUOMAS T. RISSANEN1 AND SEPPO YLA-HERTTUALA1'2'3

1 Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland 2Department of Medicine, University of Kuopio, Finland 3Gene Therapy Unit, Kuopio University, Kuopio, Finland

Abstract: Viral vectors are essential for effective transgene expression in vivo. Revascularisation therapies of ischemic tissues with adenoviruses, the most commonly used vectors for gene therapy trials, encoding angiogenic growth factors remain an intriguing option for patients who cannot be treated with conventional revascularisation therapies. Adenoviruses yield very high, but transient, gene expression and are very effective in preclinical angiogenic gene therapy trials. Studies of angiogenic growth factors using adenoviral vectors in rabbit skeletal muscle have shown that even 30-fold increases in muscle perfusion can be achieved. Such increases have not been reported with any other vector or transfection technique. In clinical trials adenoviruses have been well tolerated and safe. However, only a very few positive results on clinical endpoints have been reported. In this chapter we summarise basic knowledge about adenoviruses, their strengths and weaknesses, and discuss how the strengths of adenoviruses could be better exploited to achieve positive results in future clinical trials

Keywords:

Adenoviruses, VEGF, Gene Transfer, Gene Therapy, Gene expression

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