Antisense Inhib of Vascular Endothelial Growth Factors

Angiogenesis is a tightly regulated process which plays a role in normal physiological events such as wound healing. Angiogenesis is involved in pathological diseases such as diabetic retinopathy, rheumatoid arthritis, psoriasis, and is a key event in the growth and development of solid tumors. There are currently no effective treatments for the aberrant angiogenesis associated with these pathological diseases. Vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, has been isolated and shown to be expressed in a variety of tumor cell lines. Recently, researchers have discovered that VEGF is expressed in specific malignant cells in glioblastoma multiform in vivo , providing further evidence for the role of VEGF in tumorigenesis. The goal is the inhibition of angiogenesis using antisense technology to modulate the expression of VEGF. Specifically, we will use chemically modified antisense oligomers (e. g., phosphorothioate) to inhibit VEGF expression in murine and human cell lines known to express VEGF. Inhibition of VEGF expression will be determined by analysis of protein secretion and mRNA levels as well as by a functional in vivo bioactivity assay. The specificity of VEGF for endothelial cells makes down regulation of this molecule an attractive target for the inhibition of angiogenesis in pathological processes. This research allows for the development of novel treatments to slow the unregulated angiogenesis associated with tumor growth and other diseases.