Gene Therapy for Chronic HBV—Can We Eliminate cccDNA?

Bloom, Kristie; Maepa, Mohube Betty; Ely, Abdullah; Arbuthnot, Patrick

Several novel anti-HBV therapeutics are in preclinical development or early clinical trial (reviewed by [15, 16] ). Most candidate drugs are small molecule drugs designed to impede various stages of HBV replication. Affordable next-generation NAs, which inhibit the viral polymerase with reduced toxicity and higher barriers to HBV resistance are currently the preferred first-line of therapy. Other direct-acting antivirals include HBV core protein allosteric modulators [17, 18] , HBV surface antigen (HBsAg) release inhibitors [19, 20] and nucleic acid polymers which also inhibit viral entry [21] . With the discovery that the sodium taurocholate co-transporting polypeptide (NTCP) facilitates HBV entry into hepatocytes [22] , peptide inhibitors such as Myrcludex-B (NCT02881008 and NCT02888106) are also being developed for therapeutic application [23] . Another popular host-related strategy has been to recondition the immune system using interferons, cytokines, and peptides as immune modulators which are discussed in more detail below (Section 3.3).