VIPER

About

Overview Toll-like receptor 4 (TLR4) recognises pathogens leading to activation of the immune response, but also contributes to the development of a number of autoimmune and inflammatory diseases. As such, it has become a new target for drug development. Over millennia, viruses have optimised their ability to inhibit the immune response. Thus, the Vaccinia virus protein A46 displays a remarkable ability to inhibit TLR4 function. We have exploited this viral know-how and developed an 11-amino acid peptide from A46, termed VIPER, which, when fused to a cellpenetrating delivery sequence, potently and specifically inhibits TLR4-mediated responses in vitro and in vivo. Advantages VIPER most likely represents a surface of A46 that has been optimised by the virus to potently inhibit TLR4, so has already been through a ‘naturally occurring drug development programme’. VIPER is more effective at inhibiting TLR4 than other currently used peptide inhibitors of TLR4, in that it is more specific, more potent, less toxic, and is effective in primary human cells. Possible Applications Experimental tool for exploring TLR4 complex formation and signalling, for analysing the role of TLR4 in in vivo models of disease andfor predicting a role for Mal or TRAM in a disease process. Development as a therapeutic agent, for example by developing it into a peptidomimetic. Analysis of surfaces on Mal and TRAM targeted by VIPER as drugable sites during inflammation. Technology and Patent Status VIPER is at the product development stage. PCT application E2009/000080 has been nationalised in the following countries: US, Europe & Canada. The Opportunity VIPER is available for immediate license. Work is ongoing to develop VIPER into Mal- and TRAM-specific inhibitors, and also to further investigate its in vivo efficacy in disease models. Sample products are available on request. Further technical information on VIPER can be found in Lysakova-Devine et al (2010) J. Immunol. 185: 4261-4271.