Human papillomavirus vectors for the episomal transduction of host cells and method of making same

The present invention relates to modified human papillomavirus vectors and to methods of making and using the same, as non-integrating episomal plasmids and to certain DNA sequences, inserted therein or expressed within a host cell of the viral vector. In particular, the invention relates to a papillomavirus, in particular human papillomavirus, in which a naturally occurring genome of the virus has been altered ("HPV vector"); to methods of making a vector and transducing cells therewith; to assure persistence of a vector, as an autonomous, extrachromosomal replicon maintained by the viral E1 and E2 replication proteins, despite the removal of all viral immortalization and transformation genes; and to certain DNA sequences inserted into or expressed in a host cell by way of an HPV vector, for purposes of long term gene transduction and expression for applications in genetic modification and therapy. A replicon for delivery of a transgene for episomal gene expression in a mammalian host cell includes a transgene having an open reading frame or other nucleic acid sequence for transcription into RNA and under the transcriptional control of a first surrogate promoter and a first gene sequence expressing a papillomavirus replication initiator protein E1 tinder tile control of a second surrogate promoter. The replicon also includes second gene sequence expressing the papillomavirus replication origin binding protein E2 under the control of a third surrogate promoter, wherein tile transgene, the first and the second sequences are incorporated within at least one plasmid and less than three plasmids.