Vector-based RNAi, a novel tool for isoform-specific knock-down of VEGF and anti-angiogenesis gene therapy of cancer.
Vascular endothelial growth factor (VEGF) carries out multifaceted functions in tumor development, and it exists as at least five isoforms with distinct biologic activities and clinical implications. Several strategies have been developed to block VEGF for cancer therapy; however, the approach to target-specific VEGF isoform(s) has not been explored to date. In the present study, we show that DNA vector-based RNA interference (RNAi), in which RNAi sequences targeting murine VEGF isoforms are inserted downstream of an RNA polymerase III promoter, has potential applications in isoform-specific "knock-down" of VEGF. Large molecular weight VEGF isoforms were specifically reduced in vitro in the presence of isoform-specific RNAi constructs. Additionally, H1 promoter may be superior to U6 promoter when used for vector-based RNAi of VEGF isoforms. This strategy provides a novel tool to study the function of various VEGF isoforms and may contribute to VEGF isoform-specific treatment in cancer.
Zhang
Lin
L
Abramson Family Cancer Research Institute, Philadelphia, PA 19104, USA.
Yang
Nuo
N
Mohamed-Hadley
Alisha
A
Rubin
Stephen C
SC
Coukos
George
G
D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000628:therapy; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics; D012334:RNA, Neoplasm / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D012330:RNA, Double-Stranded; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D049452:Green Fluorescent Proteins