Modified clostridial toxins with enhanced translocation capabilitiy

Abstract

The specification discloses modified Clostridial toxins comprising a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain, a translocation facilitating domain and an enhanced targeting domain; polynucleotide molecules encoding such modified Clostridial toxins; and method of producing such modified Clostridial toxins.

What is claimed: 
     
         1 . A polynucleotide molecule encoding a modified botulinum toxin, the modified botulinum toxin comprising:
 a) a botulinum toxin enzymatic domain capable of executing an enzymatic target modification step of a botulinum toxin intoxication process;   b) a botulinum toxin translocation domain capable of executing a translocation step of a botulinum toxin intoxication process;   c) a translocation facilitating domain capable of facilitating a translocation step of a botulinum toxin intoxication process;   d) an enhanced targeting domain comprising a modified botulinum H CC  targeting domain capable of executing a cell binding step of a botulinum toxin intoxication process; and   e) a protease cleavage site;   wherein cleavage of the protease cleavage site converts the single-chain form of the modified botulinum toxin into the di-chain form; and   wherein the modified botulinum H CC  targeting domain exhibits enhanced binding activity for an endogenous botulinum toxin receptor relative to the binding activity of a naturally-occurring botulinum H CC  targeting domain from which the modified botulinum H CC  targeting domain is derived.