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

Parry TJ, T J Parry, C Cushman, Cushman C, Gallegos AM, A M Gallegos, A B Agrawal, Agrawal AB, Richardson M, M Richardson, Andrews LE, L E Andrews, Maloney L, L Maloney, Mokler VR, V R Mokler, F E Wincott, Wincott FE, P A Pavco, Pavco PA
Nucleic acids research · 1999 · vol. 27(13) , pp. 2569–77 · doi:10.1093/nar/27.13.2569 · PMID:10373571 · PMC148463
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Ribozymes targeting Flt-1 and KDR mRNA reduced VEGF-induced endothelial cell proliferation and exhibited anti-angiogenic activity in a rat corneal pocket assay, demonstrating their potential for studying VEGF receptor function.

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Abstract

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.

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MeSH descriptors

Endothelium, Vascular Proto-Oncogene Proteins Receptor Protein-Tyrosine Kinases Receptors, Growth Factor RNA, Catalytic Animals Endothelium, Vascular Endothelium, Vascular Gene Expression Regulation Gene Expression Regulation Gene Targeting Humans Male Neovascularization, Pathologic Neovascularization, Pathologic Neovascularization, Pathologic Neovascularization, Physiologic Neovascularization, Physiologic Proto-Oncogene Proteins Rats

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