Stabilization of Therapeutic Agents to Facilitate Administration

Abstract

The present invention provides for a carrier complex for administration of therapeutic agents. In one aspect, an isolated C. botulinum carrier complex is provided, where the carrier complex lacks a native neurotoxin subunit.

1 . An isolated  Clostridium botulinum  carrier complex, wherein the carrier complex lacks a native neurotoxin subunit and said carrier complex is capable of reversibly and controllably alternating between an open and a closed conformation. 
     
     
         2 . The complex of  claim 1 , wherein said carrier complex further comprises a non-native therapeutic molecule. 
     
     
         3 . The complex of  claim 1 , wherein said carrier complex further comprises a ligand. 
     
     
         4 . The complex of  claim 1 , wherein said carrier complex further comprises a therapeutic agent and a ligand. 
     
     
         5 . The complex of  claim 1 , wherein said carrier complex is a variant carrier complex. 
     
     
         6 . The complex of  claim 5 , wherein said carrier complex further comprises a non-native therapeutic molecule. 
     
     
         7 . The complex of  claim 1 , wherein said carrier complex comprises a non-toxin non hemagglutinin subunit and a non-toxin hemagglutinin subunit. 
     
     
         8 . The complex of  claim 1 , further comprising a non-native neurotoxin subunit. 
     
     
         9 . The complex of  claim 1 , wherein said carrier complex comprises a non-toxin non hemagglutinin subunit and a non-toxin hemagglutinin subunit. 
     
     
         10 . A method of purifying a carrier complex derived from  Clostridium botulinum , the carrier complex lacking a native  botulinum  neurotoxin subunit, comprising:
 (a) isolating a native multi-subunit complex;   (b) disassociating the native multi-subunit complex into its constituent subunits;   (c) separating the native  botulinum  neurotoxin subunit therefrom; and   (d) re-associating remaining subunits into the carrier complex, thereby producing a carrier complex lacking a native  botulinum  neurotoxin subunit.   (e) A carrier complex provided by the method of  claim 10 .   
     
     
         11 . The method of  claim 10  further comprising the step of associating a non-native therapeutic molecule to the carrier complex covalently. 
     
     
         12 . A modified organism producing a carrier complex, said carrier complex comprising a non-toxin non hemagglutinin subunit and a non-toxin hemagglutinin subunit, wherein said carrier complex lacks a neurotoxin subunit. 
     
     
         13 . The organism of  claim 12 , wherein the carrier complex further comprises a non-native neurotoxin subunit having a non-native binding moiety. 
     
     
         14 . A modified  Clostridium botulinum  bacteria expressing a variant carrier complex, wherein the variant carrier complex lacks a neurotoxin subunit. 
     
     
         15 . The organism of  claim 12 , wherein the organism is a modified  Clostridium botulinum .