PERSPECTIVES O

ne of the major enigmas in hepatitis B virus (HBV) infection is the strik-ing persistence of its episomal DNA [covalently closed circular DNA (cccDNA)], the viral transcriptional template sequestered in the nucleus of infected hepatocytes. Eradi-cating cccDNA is a requisite for virus elim-ination and cure, a desirable end point for the 400 million people chronically infected by HBV worldwide who are at a substan-tial risk for end-stage liver disease and liver cancer. Commonly used therapies suppress viral replication, but because they are inef-fective at targeting the cccDNA pool, they often require lifelong administration to pre