Background and ObjectiveVascular endothelial growth factor (VEGF) has been implicated as a critical molecular signal in malignant solid human tumors development. Inhibition of VEGF to interfere with tumor neovascularization is one of the most important strategies in anti-angiogenesis therapy. Various VEGF-targeting approaches have been developed and some of them are in clinical trials, including small molecule inhibition of VEGF-receptors, dominant negative VEGF, humanized antibodies to VEGF, soluble VEGF receptors, antisense oligonucleotide, as well as ribozyme technologies against VEGF. However, except for antisense approach, the above strategies are incapable of specific targeting of VEGF; and even the efficiency of antisense is usually very low. RNA interference (RNAi) is a sequence-specific posttranscriptional gene silencing mechanism, which is triggered by double-stranded RNA (dsRNA) and causes degradation of mRNA homologous in sequence to the dsRNA. This new approach has been successfully applied to inhibit virus replication and tumorigenicity. RNAi may provide a more powerful strategy than ever before to inhibit tumor angiogenesis through a nucleic acid drug or a gene therapy approach. |