Modulation of angiogenesis with siRNA inhibitors for novel therapeutics.
Cancer and many other serious diseases are characterized by the uncontrolled growth of new blood vessels. Recently, RNA interference (RNAi) has reinvigorated the therapeutic prospects for inhibiting gene expression and promises many advantages over binding inhibitors, including high specificity, which is essential for targeted therapeutics. This article describes the latest developments using small-interfering RNA (siRNA) inhibitors to downregulate various angiogenic and tumor-associated factors, both in cell-culture assays and in animal disease models. The majority of research efforts are currently focused on understanding gene function, as well as proof-of-concept for siRNA-mediated anti-angiogenesis. The prospects for siRNA therapeutics, both advantages and looming hurdles, are evaluated.
Lu
Patrick Y
PY
Intradigm Corporation, 12115 K Parklawn Drive, Rockville, MD 20852, USA. patricklu@intradigm.com
Xie
Frank Y
FY
Woodle
Martin C
MC
D015815:Cell Adhesion Molecules / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000503:physiopathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015815:Cell Adhesion Molecules; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases