Methods and compositions for genomic integration

A method of expressing an exogenous human therapeutic polypeptide from a genomically integrated DNA sequence of a target human cell, the method comprising:

• (a) contacting a composition to the target human cell, the composition comprising one or more RNA molecules, wherein the target human cell uptakes the one or more RNA molecules, and wherein the one or more RNA molecules comprise an RNA sequence that comprises:
• (i) a sequence that is a reverse complement of a DNA sequence that encodes human therapeutic polypeptide;
• and
• (ii) a human mobile genetic element, wherein the human mobile genetic element comprises (I) an RNA sequence encoding a polypeptide with target-primed reverse transcription (TPRT) activity, and (II) an RNA sequence encoded by a sequence having at least 80% sequence identity to SEQ ID NO:
• 58;
• (b) translating the RNA sequence encoding the polypeptide with TPRT activity and translating the RNA sequence encoded by a sequence having at least 80% sequence identity to SEQ ID NO:
• 58;
• (c) reverse transcribing the sequence that is the reverse complement of the DNA sequence that encodes human therapeutic polypeptide via the TPRT activity of the polypeptide with TPRT activity translated in step (b), thereby producing a DNA sequence encoding the exogenous human therapeutic polypeptide;
• (d) integrating the DNA sequence encoding the exogenous human therapeutic polypeptide produced in step (c) into genomic DNA of the target human cell;
• and
• (e) expressing the exogenous human therapeutic polypeptide in the target human cell, wherein the exogenous human therapeutic polypeptide is expressed from the DNA sequence integrated into the genomic DNA of the target human cell in step (d).