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靶向Flt-1和KDR mRNA的抗血管生成核酶的生物活性

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

作者信息

Parry T J, Cushman C, Gallegos A M, Agrawal A B, Richardson M, Andrews L E, Maloney L, Mokler V R, Wincott F E, Pavco P A

机构信息

Ribozyme Pharmaceuticals, Inc., 2950 Wilderness Place, Boulder, CO 80301, USA and.

出版信息

Nucleic Acids Res. 1999 Jul 1;27(13):2569-77. doi: 10.1093/nar/27.13.2569.

DOI:10.1093/nar/27.13.2569

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC148463/

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.

摘要

血管内皮生长因子（VEGF）及其受体Flt-1和KDR在生理和病理血管生成中发挥重要作用。已开发出靶向VEGF受体mRNA的核酶，并评估了它们在细胞培养和动物模型中的生物学活性。靶向Flt-1或KDR mRNA位点的核酶降低了VEGF诱导的人血管内皮细胞培养物的增殖，并特异性降低了细胞中存在的Flt-1或KDR mRNA水平。在VEGF诱导的血管生成的大鼠角膜袋试验中，抗Flt-1和KDR核酶也表现出抗血管生成活性。本报告阐述了这些核酶的抗血管生成潜力及其在研究正常和病理生理状态下VEGF受体功能方面的价值。