Bioactivity of anti-angiogenic ribozymes targeting Flt-1 and KDR mRNA.
Vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR play important roles in physiological and pathological angiogenesis. Ribozymes that target the VEGF receptor mRNAs were developed and their biological activities in cell culture and an animal model were assessed. Ribozymes targeting Flt-1 or KDR mRNA sites reduced VEGF-induced proliferation of cultured human vascular endothelial cells and specifically lowered the level of Flt-1 or KDR mRNA present in the cells. Anti- Flt-1 and KDR ribozymes also exhibited anti-angiogenic activity in a rat corneal pocket assay of VEGF-induced angiogenesis. This report illustrates the anti-angiogenic potential of these ribozymes as well as their value in studying VEGF receptor function in normal and pathophysiologic states.
Parry
T J
TJ
Ribozyme Pharmaceuticals, Inc., 2950 Wilderness Place, Boulder, CO 80301, USA and.
Cushman
C
C
Gallegos
A M
AM
Agrawal
A B
AB
Richardson
M
M
Andrews
L E
LE
Maloney
L
L
Mokler
V R
VR
Wincott
F E
FE
Pavco
P A
PA
D000818:Animals; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D018390:Gene Targeting; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016337:RNA, Catalytic / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1
D011518:Proto-Oncogene Proteins; D016337:RNA, Catalytic; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1