title: Differing prospects for the future of using gene therapy to treat infections with hepatitis B virus and hepatitis C virus.
abstract: Infections with hepatitis B and hepatitis C viruses (HBV and HCV) are major global causes of liver diseases, often become chronic, and may be complicated by cirrhosis and liver cancer. Although HBV and HCV share common clinical features, their molecular biology is very different. HBV is a DNA virus that replicates by a mechanism that involves reverse transcription. The replication intermediate comprising nuclear covalently closed circular DNA (cccDNA) is stable and is largely unaffected by currently licensed drugs. Disabling cccDNA using gene therapy, particularly through application of gene editing technology, shows promise. Advancing this strategy may lead to a cure of HBV infection. HCV differs from HBV in that it is an RNA virus that replicates exclusively in the cytoplasm of infected cells. RNAi-based gene silencing and inhibition of the function of microRNA-122 using antisense oligonucleotides have shown promise against HCV. However recent evidence indicates that HCV may be eliminated with a combination of drugs that achieves sustained inhibition of viral replication and provides a high barrier to viral resistance. The long term prospects of nucleic acid-based HCV treatment are likely to be influenced by the success and affordability of these directly acting small molecule drugs. Conversely, since HBV is not susceptible to elimination using a similar approach, developing gene therapy for HBV infection remains a priority.
authors.affiliation: Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Health Sciences Faculty, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Ely
authors.affiliation: Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Health Sciences Faculty, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Patrick
authors.initials: P
authors.lastname: Arbuthnot
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism; D004267:DNA Viruses; D004270:DNA, Circular; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods*; D016174:Hepacivirus; D006509:Hepatitis B / Q000628:therapy* / Q000821:virology; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000821:virology; D006526:Hepatitis C / Q000628:therapy* / Q000821:virology; D006801:Humans; D008099:Liver / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000235:genetics; D015202:Protein Engineering; D034622:RNA Interference; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D004270:DNA, Circular; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense