Bioactivity of anti-angiogenic ribozymes targeting Flt-1 and KDR mRNA

Vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR p lay important roles in physiological and pathological angiogenesis, Ribozym es that target the VEGF receptor mRNAs were developed and their biological activities in cell culture and an animal model were assessed. Ribozymes tar geting Flt-1 or KDR mRNA sites reduced VEGF-induced proliferation of cultur ed human vascular endothelial cells and specifically lowered the level of F lt-1 or KDR mRNA present in the cells, Anti-Nt-l and KDR ribozymes also exh ibited anti-angiogenic activity in a rat corneal pocket assay of VEGF-induc ed angiogenesis. This report illustrates the anti-angiogenic potential of t hese ribozymes as well as their value in studying VEGF receptor function in normal and pathophysiologic states.