Angiogenesis is a common process that is essential for tumor growth beyond 2 mm. Although numerous growth factors are involved, vascular endothelial growth factor (VEGF), particularly VEGF-A, has been shown to play an important role in tumor angiogenesis.
RNAi technology is evaluated not only as an extremely powerful instrument for functional genomic analyses but also as a potentially useful method to develop highly specific gene silencing therapeutic.
A research article to be published October 28 in the World Journal of Gastroenterology addresses the above issue. In this study, the researchers constructed vector-based expression systems in which sense and antisense strands of short VEGF sequences were transcribed into the hairpin structure under the control of the U6 promoter.
They demonstrate that siRNAs which targeted against VEGF efficiently reduced the transcript levels of VEGF mRNAs, ultimately resulting in a reduction in the levels of VEGF protein. Furthermore, this inhibition was shown to be highly selective and sequence-specific because control siRNAs had little inhibitory effects on expression and transcription of VEGF.
The researchers have further demonstrated that, in addition to the above-reported target sites in the VEGF genome, the specific 21-bp siRNAs targeting VEGF exerted efficient and specific inhibition on VEGF expression, suggesting a good method to inhibit the expression of VEGF.
Future studies will be centered on the evaluation of the anti-VEGF efficacy of RNAi vectors in valid animal models, as well as on the preclinical elucidation using the RNAi technology.