Regulation of vascular endothelial growth factor gene under hypoxia by using artificial transcription factors.

The vascular endothelial growth factor A (VEGF-A) gene is an attractive therapeutic target because both activation and repression of the gene are useful for treatment or cure of many diseases related to abnormal angiogenesis. To up- or downregulate the endogenous gene expression at will, we previously designed a 6-finger AZP to recognize a 19-bp target DNA in the VEGF-A gene, and fused the AZP with a nuclear localization signal and a transcriptional regulatory domain to generate artificial transcription factors (ATFs) for VEGF-A. Using the ATFs, we previously demonstrated efficient modulation of the endogenous VEGF-A expression under normoxia. In the present study, we examined whether these ATFs modulate the endogenous VEGF-A gene expression under hypoxic conditions as well. Enzyme-linked immunosorbent assays revealed that the gene-delivered ATFs up- or downregulated the VEGF-A expression efficiently under hypoxia.