FUSION PROTEINS

摘要

A single chain, polypeptide fusion protein, comprising: a non-cytotoxic
protease, 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 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 nociceptive sensory afferent.
Nucleic acid sequences encoding the polypeptide fusion proteins, methods of
preparing same and uses thereof are also described.