Gene Therapy for Chronic HBV—Can We Eliminate cccDNA?

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

Other challenges, which are broadly associated with implementing gene-based therapies [107] , also need to be met for the approach to be successful against HBV. Efficient liver-specific delivery using viral or non-viral vectors still remains a challenge [108, 109] . This will be particularly important if multiple doses of gene therapy are required. Improving DNA-binding specificity, particularly for designer nucleases, and defining off target effects are vital to limit unintended side effects [110] . The lack of suitable chronic HBV infection models also complicates the development of gene therapies for the treatment of the disease. The CRISPR/Cas9 system has been shown to target cccDNA efficiently in primary duck hepatocytes infected with DHBV [65] . Although DHBV infection of ducks provides a useful model of chronic HBV infection, it does not recapitulate all aspects of the condition in humans. Despite the challenges facing clinical translation of gene-based curative therapy for chronic HBV infection, the field is gaining momentum and significant progress seems imminent.