siRNA-mediated inhibition of angiogenesis

Small interfering RNA (siRNA) has rapidly become the agent of choice for gene function analysis through loss-of-function phenotypes. Especially in complicated (patho)physiological processes such as angiogenesis, where vast numbers of proteinaceous factors are involved, the siRNA application allows relatively fast analysis of pathways and identification of new target genes. The first studies on the therapeutic effects of siRNA in angiogenesis show that this new 'drug' class holds great promise for therapeutic intervention. Two strategies emerge: the use of unmodified or the use of complexed, targeted and/or protected nucleic acids. The challenge for clinical application will be to control off-target effects and the transient character of the sequence-specific silencing effect, and to address the targeted delivery to the cell types involved in the various stages of angiogenesis. This is especially important as clinical studies indicate a profound heterogeneity of the angiogenic vasculature.