The invention pertains to methods of delivering a polypeptide to a cell comprising (a) contacting a cell with a replicon having a non-poliovirus nucleic acid substituted for a nucleic acid which encodes at least a portion of a protein necessary for encapsidation, the non-poliovirus nucleic acid encoding, in an expressible form, a polypeptide or fragment thereof; and (b) maintaining the cells under conditions appropriate for introduction of the replicons into the cells. The cell may be within a subject and the polypeptide may be a therapeutic agent. The methods of the invention may be used to treat diseases including central nervous system disorders, infectious diseases, and cancer.