Sequence- and target-independent angiogenesis suppression by siRNA via TLR3

Generic, not sequence- or targeted, SiRNA prevents Age Related Macular Degeneration and can potentially treat Angiogenic Disorders.

Posted by: Mondar M. M. Ahmed
Student Number: 41280337
University of Queensland

Choroidal neovasculasation (CNV) is the formation of new blood vessels in the choroidal layer of the eye that leads to blurring of the central vision or age related macular degeneration. The formation of the new vessels is associated with elevated amounts of Vascular Endothelial Growth Factor (VEGF). Photodynamic drugs are used to treat the disease by breaking down the new vessels and preventing neovascularisation. Anti-VEGF drugs are also used. SiRNAs targeting the VEGFA or its receptor VEGFR1 are also being investigated as a potential route to stopping CNV.


SiRNAs are small interfering RNAs which silence genes by RNA interference. Previously it was thought that sequence specific targeted SiRNA prevented CNV by gene silencing. However, this thorough study by Kleinman et. al. has demonstrated that suppression is not mediated by gene silencing using specific SiRNA but rather is a class effect of generic SiRNAs at least 21 nucleotides long. These generic SiRNAs can suppress CNV mediated by toll-like receptor 3 (TLR3) on the cell surface and its adaptor called TRIF with induction of anti-angiogenic innate immunity via IFN-γ and IL-12. The study opens a new avenue for the treatment of angiogenic disorders, that is, it may be possible to treat other forms of angiogenic disorders using the generic SiRNAs which work as well as VEGFA antibodies and are less toxic.

(Click on eye to see animation.)