title: Advances with using CRISPR/Cas-mediated gene editing to treat infections with hepatitis B virus and hepatitis C virus.
abstract: Chronic infections with hepatitis B and hepatitis C viruses (HBV and HCV) account for the majority of cases of cirrhosis and hepatocellular carcinoma. Current therapies for the infections have limitations and improved efficacy is necessary to prevent complications in carriers of the viruses. In the case of HBV persistence, the replication intermediate comprising covalently closed circular DNA (cccDNA) is particularly problematic. Licensed therapies have little effect on cccDNA and HBV replication relapses following treatment withdrawal. Disabling cccDNA is thus key to curing HBV infections and application of gene editing technology, such as harnessing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, has curative potential. Several studies have reported good efficacy when employing CRISPR/Cas technologies to disable HBV replication in cultured cells and in hydrodynamically injected mice. Recent advances with HCV drug development have revolutionized treatment of the infection. Nevertheless, individuals may be refractory to treatment. Targeting RNA from HCV with CRISPR/Cas isolated from Francisella novicida may have therapeutic utility. Although preclinical work shows that CRISPR/Cas technology has potential to overcome infection with HBV and HCV, significant challenges need to be met. Ensuring specificity for viral targets and efficient delivery of the gene editing sequences to virus-infected cells are particularly important. The field is at an interesting stage and the future of curative antiviral drug regimens, particularly for treatment of chronic HBV infection, may well entail use of combinations that include derivatives of CRISPR/Cas.
authors.affiliation: Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Buhle
authors.initials: B
authors.lastname: Moyo
authors.affiliation: Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Kristie
authors.initials: K
authors.lastname: Bloom
authors.affiliation: Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa; Center for Gene Therapy, Beckman Research Institute of City of Hope, Duarte, CA, USA.
authors.forename: Tristan
authors.initials: T
authors.lastname: Scott
authors.affiliation: Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Science, 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, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: Patrick.Arbuthnot@wits.ac.za.
authors.forename: Patrick
authors.initials: P
authors.lastname: Arbuthnot
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D000076987:CRISPR-Associated Protein 9; D064113:CRISPR-Cas Systems; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D053837:DNA Cleavage; D004270:DNA, Circular / Q000235:genetics* / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000628:therapy* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000628:therapy* / Q000821:virology; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D061214:Patient Safety; D000094704:RNA, Guide, CRISPR-Cas Systems / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D001426:Bacterial Proteins; D004270:DNA, Circular; D004279:DNA, Viral; D000094704:RNA, Guide, CRISPR-Cas Systems; D000076987:CRISPR-Associated Protein 9; C000600049:Cas9 protein, Francisella novicida; D004720:Endonucleases
keywords: CRISPR/Cas; Gene therapy; HBV; HCV; cccDNA