Pannexin1 (Panx1) channels mediate the exchange of biochemical messengers between the cytosol of a cell and its extracellular environment. This type of cellular communication underlies cell death and inflammation, both which are associated with a plethora of diseases. Closing pannexin channels therefore seems an interesting therapeutic strategy. In this respect, the ERC Starting Grant project CONNECT has demonstrated that peptide-based inhibition of Panx1 channels counteracts the manifestation of acute and chronic liver disease. However, these peptides cope with stability issues thus impeding clinical application. No other types of appropriate Panx1 channel inhibitors are available today despite their promising therapeutic potential. The present CONNECT-2-CLINIC project meets this urgent need by generating specific and in vivo-applicable Panx1 channel inhibitors. For this purpose, nanobodies targeted towards Panx1 are produced using unprecedented protocols. Panx1 nanobodies are tested in vitro for their capacity to selectively inhibit Panx1 channels. They are subsequently tested in a human-relevant mouse model of inflammatory liver disease. This technology track is aligned by a 3-phase business track in order to analyze and create market value. By doing so, the CONNECT-2-CLINIC project provides solid proof-of-concept for further pharmaceutical development and clinical application.
