Methods and compositions are provided for delivery of therapeutic nucleic acidsto a target cell. A chimeric antigen is provided to encapsulate, bind, or otherwisecarry a nucleic acid molecule to a target cell where the chimeric antigen and nucleicacid are internalized by receptor-mediated endocytosis. The chimeric antigenhas a nucleic acid interaction domain, a target binding domain, and an immuneresponse domain that may include a target antigen. Targeting is generally providedby 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 immuneresponse domain. The combined delivery of chimeric antigen and nucleic acid,which may be a siRNA, may be synergistic in certain applications, for examplein breaking host tolerance to a virus or in providing immunostimulation.
