Chronic HBV affects 296M globally, with 1.5M new cases yearly, due to the persistence of cccDNA, which is the main barrier to a cure (WHO, 2023; Revill et al., 2020). We propose a systematic review of 500+ studies to identify cccDNA vulnerabilities and rank therapies. These include CRISPR-Cas9 for DNA cleavage (Lucifora et al., 2014), RNAi for gene silencing (Guo et al., 2021), and epigenetic drugs for transcriptional silencing (Belloni et al., 2012).