The invention provides a vector encoding a derivative of EBNA-1 that is not cytotoxic when expressed efficiently in cells, which supports extrachromosomal replication, maintenance and transcription from extrachromosomal oriP containing vectors but does not substantially activate transcription from host cell genes. Also provided is a vector having oriP and encoding a derivative of EBNA-1. The vectors of the invention may be employed in vitro and in gene therapy.