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 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.
