Fusion proteins

摘要

A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, 5 or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a 10 protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is 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 15 nociceptive sensory afferent; wherein the Targeting Moiety is selected from the group consisting of BAM, p-endorphin, bradykinin, substance P, dynorphin and/or nociceptin. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.