Chronic Hepatitis B virus (HBV) infection is a significant global health issue, affecting approximately 254 million people and resulting in 1.1 million deaths annually. While nucleos(t)ide analogs control virus replication, they do not cure HBV and require lifelong treatment. Therefore, there is an urgent need to develop a curative therapy. To directly target HBV that persists episomally, it is essential to have an in vitro system where an HBV episome is present and replicated in every hepatocyte as in natural infection. In this study, we took advantage of plasmid pEpi in which a matrix attachment region sequence allows episomal persistence and replication in a copy number of 5-10 molecules per cell comparable to episomal HBV-DNA in infected hepatocytes. We integrated a replication-competent 1.3-fold HBV genome and created a stable cell line, Huh7-pEpiH1.3, and showed that they support the full life cycle of HBV and produce infectious virus from the episome. To target HBV therapeutically, we designed guide RNAs (gRNAs) compatible with cytosine base editors (CBEs) and adenosine base editors (ABEs) that enable precise DNA base conversions, allowing for the generation of missense and nonsense mutations without causing double-stranded breaks in the HBV genome. The in-silico design of gRNAs ensures compatibility with the predominant HBV genotypes circulating globally. Our novel Huh7-pEpiH1.3 screening system will allow the identification of the most effective gRNAs. We aim to validate our findings in hepatoma cell lines,  primary human hepatocytes infected with HBV and in in-vivo models of HBV infection.