The proposal will use a significant and potentially transformational approach to genome engineering of herpesviruses by using new and novel synthetic genomics methods. The goal is to use the more “tractable” herpes simplex virus type 1 (HSV-1) genome to establish and refine synthetic genomics engineering methods and then use that information to build a wild-type infectious clone of Epstein-Barr virus (EBV) that is stable and which can be engineered using synthetic biology.