Compositions and methods are provided for achieving persistent, high level expression of transgenes in vitro and in vivo. Aspects of the invention include vectors comprising an intronic cassette that comprises plasmid elements, and methods that rely on the use of vectors comprising an intronic cassette that comprises plasmid elements. These compositions and methods find use in many applications, including therapeutic applications such as in gene therapy synthesis applications such as in the synthesis of peptides, proteins, and RNAs, e.g. for research or therapeutic purposes and research applications, such as in the production of transgenic cells and animals. In addition, reagents, devices and kits thereof that find use in making the subject compositions and practicing the subject methods are provided.
