Antigenic compositions and use of same in the targeted delivery of nucleic acids

Abstract

Methods and compositions are provided for delivery of therapeutic nucleic acids to a target cell. A chimeric antigen is provided to encapsulate, bind, or otherwise carry a nucleic acid molecule to a target cell where the chimeric antigen and nucleic acid are internalized, for example by receptor-mediated endocytosis. The chimeric antigen has a nucleic acid interaction domain, a target binding domain, and an immune response domain that may include a target antigen. Targeting is generally provided by the specificity of the target binding domain for a particular target cell receptor, but may also be provided by inclusion of a targeting antigen within the immune response domain. The combined delivery of chimeric antigen and nucleic acid, which may be a siRNA, may be synergistic in certain applications, for example in breaking host tolerance to a virus or in providing immunostimulation.

1 .- 38 . (canceled) 
     
     
         39 . A fusion protein comprising:
 (a) a target binding domain for binding to a receptor on the surface of the target cell, the target binding domain comprising an antibody fragment comprising the hinge region, at least a portion of a C H 1 region and an Fc fragment comprising a C H 2 and a C H 3 domain;   (b) an immune response domain operatively attached to the target binding domain;   (c) a first nucleic acid interaction domain corresponding to a HBV core protein or a fragment thereof operatively attached to the immune response domain; and   (d) a second nucleic acid interaction domain operatively attached at the C-terminus of the target binding domain corresponding to the HBV core protein or a fragment thereof having at least the protamine domain of the HBV core protein.   
     
     
         40 . The fusion protein of  claim 39 , wherein the target binding domain is a xenotypic antibody fragment. 
     
     
         41 . The fusion protein of  claim 39 , wherein the immune response domain comprises an antigenic amino acid sequence. 
     
     
         42 . The fusion protein of  claim 39 , wherein the immune response domain provides targeting to a secondary target cell. 
     
     
         43 . The fusion protein of  claim 39 , wherein the first nucleic acid binding domain comprises a fragment of the assembly domain of the HBV core protein and wherein the second nucleic acid binding domain comprises a fragment of the assembly domain and the protamine domain of the HBV core protein. 
     
     
         44 . The fusion protein of  claim 39 , wherein the first nucleic acid binding domain comprises at least amino acids 1 to 78 of the HBV core protein (SEQ ID NO:2) and wherein the second nucleic acid binding domain comprises at least amino acids 81 to 183 of the HBV core protein (SEQ ID NO:2).