Recent major improvements in synthetic DNA vaccine technology have changed our view of the use of this platform to impact infectious disease. Synthetic DNA has moved from a weak immune performer, to a highly consistent immune potent platform with the ability to generate protective immune responses in a rapid fashion. We present important recent examples of translational development for important targets such as HPV infection, Ebola, and Zika. Finally, the enhancement of this technology now enables an ability to launch DNA encoded MAb’s. This opens novel areas and new approaches for difficult and important disease targets