Vascular endothelial growth factor A (VEGF-A) gene and mRNA (VEGF-A)

Vascular endothelial growth factor A (VEGF-A) is a fundamental regulator of both physiological and pathological angiogenesis, vasculogenesis, and vascular permeability. While most established clinical therapies, such as bevacizumab and ranibizumab, target the secreted VEGF-A protein, the VEGF-A mRNA and its promoter DNA represent upstream therapeutic targets for gene-silencing or gene-activating modalities. Targeting the mRNA via RNA interference (siRNA) or ribozymes aims to prevent protein production at the source, a strategy primarily explored for neovascular eye diseases like age-related macular degeneration and various solid tumors. Conversely, targeting the VEGF-A promoter with engineered transcription factors or delivering modified mRNA can induce localized VEGF-A expression to promote revascularization in ischemic conditions such as peripheral artery disease or myocardial infarction. Despite the theoretical advantages of these nucleic acid-based approaches, many early candidates like bevasiranib and SB-509 faced significant challenges in clinical efficacy and delivery, leading to their discontinuation.

Other names

Vascular permeability factorVPFVEGFAVEGFVascular endothelial growth factor A geneVascular endothelial growth factor A mRNA

Modulation of VEGF-A expression through RNA interference (siRNA), ribozyme-mediated mRNA cleavage, or transcriptional regulation via promoter-binding zinc finger proteins.