A new episomal vector system shows unprecedented capability to express large, tandemly repeated proteins and multi-protein complexes in mammalian cells. The pJAZZ Epi system is based on Lucigen’s unique linear pJAZZ vector, which enables stable cloning of difficult or repetitive sequences that cannot be maintained in circular plasmids. The pJAZZ vector can accommodate payloads of 30-40 kb, allowing expression of multiple genes and multi-protein complexes. For example, cloning and expression of four direct repeats of the inositol 1,4,5-triphosphate receptor gene and production of a functional 1,000 kDa Ca⁺⁺ channel protein was possible only in the pJAZZ mammalian expression vector.¹   We are adapting the pJAZZ vector for stable maintenance as an episome in mammalian cells, circumventing the time-consuming process of generating stable cell lines by integration. We have incorporated a blue light-inducible system to permit on-demand gene expression, with spatial and temporal resolution that cannot be achieved with classical small molecule-based induction systems. In addition, we are optimizing novel fluorescent proteins (FP) as fusion partners in pJAZZ-epi for use in evaluating protein-protein interactions via Förster Resonance Energy Transfer (FRET). These new FPs have a higher FRET efficiency than conventional partners, representing a further step toward developing a FRET pair suitable for a fluorescence microplate-based assay. The pJAZZ Epi system, in conjunction with the efficient FRET FPs, will serve as a platform for new technologies, including development of HTS screens that target protein-protein interactions in vivo.