Overview of gene editing strategies against HBV

254 million people currently live with chronic hepatitis B virus (HBV) infection, with over 1 million deaths annually due to complications such as cirrhosis and hepatocellular carcinoma. Although current direct-acting antivirals suppress HBV replication, they do not eliminate the virus and rarely lead to HBV functional cure, defined as the loss of serum hepatitis B surface antigen (HBsAg) and DNA. A major barrier to achieving HBV functional cure is the HBV covalently closed circular DNA minichromosome (cccDNA), which hides from the immune system in the nucleus of an infected cell, and is very stable. Another barrier is integration of incomplete HBV genomes into the host genome, which is the main source of HBsAg in later disease stages, and is difficult to target without impacting the human genome. New direct-acting antivirals are required that target different stages of the HBV replication cycle, including the HBV cccDNA and integrated DNA to improve rates of functional cure. The development of gene editing tools provides an opportunity to develop novel therapies that target the HBV cccDNA, integrated DNA and HBV RNA. This review explores the different gene editing tools that have been used to target the HBV cccDNA, integrated DNA and RNA.