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Genes 2018, 9(4), 207; https://doi.org/10.3390/genes9040207

Gene Therapy for Chronic HBV—Can We Eliminate cccDNA?

Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS 2050, South Africa
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Received: 15 March 2018 / Revised: 5 April 2018 / Accepted: 9 April 2018 / Published: 12 April 2018
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Abstract

Chronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular DNA (cccDNA) and emergence of resistance remain the most worrisome. Viral rebound from latent episomal cccDNA reservoirs occurs following cessation of therapy, patient non-compliance, or the development of escape mutants. Simultaneous viral co-infections, such as by HIV-1, further complicate therapeutic interventions. These challenges have prompted development of novel targeted hepatitis B therapies. Given the ease with which highly specific and potent nucleic acid therapeutics can be rationally designed, gene therapy has generated interest for antiviral application. Gene therapy strategies developed for HBV include gene silencing by harnessing RNA interference, transcriptional inhibition through epigenetic modification of target DNA, genome editing by designer nucleases, and immune modulation with cytokines. DNA-binding domains and effectors based on the zinc finger (ZF), transcription activator-like effector (TALE), and clustered regularly interspaced short palindromic repeat (CRISPR) systems are remarkably well suited to targeting episomal cccDNA. This review discusses recent developments and challenges facing the field of anti-HBV gene therapy, its potential curative significance and the progress towards clinical application. View Full-Text
Keywords: hepatitis B virus; covalently closed circular DNA; gene therapy; epigenetic modification; designer nucleases hepatitis B virus; covalently closed circular DNA; gene therapy; epigenetic modification; designer nucleases
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Bloom, K.; Maepa, M.B.; Ely, A.; Arbuthnot, P. Gene Therapy for Chronic HBV—Can We Eliminate cccDNA? Genes 2018, 9, 207.

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