FUSION PROTEINS COMPRISING A NON-CYTOTOXIC PROTEASE, A TARGETING MOIETY, A PROTEASE CLEAVAGE SITE AND A TRANSLOCATION DOMAIN

摘要

The invention provides a single chain, polypeptide fusion protein, comprising: a non-cylotoxic prolease, or a fragment threrof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a target cell; a Targeting Moiety that is capable odf binding to a Binding Sire on the target cell, which Binding Site is capable of undergoing endocytosis to be ncorporated into an endosome within the target cell; a protease cleavage site at which site the fusion protein is cleavable by aprotease, wherein the protease cleavage site located between the non-cytotoxic protease or fragment thereof and the Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the target cell.