Recent developments with advancing gene therapy to treat chronic infection with hepatitis B virus.
Journal
Current opinion in HIV and AIDS
ISSN: 1746-6318
Titre abrégé: Curr Opin HIV AIDS
Pays: United States
ID NLM: 101264945
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
pubmed:
7
3
2020
medline:
10
8
2021
entrez:
7
3
2020
Statut:
ppublish
Résumé
The available vaccine and therapies against hepatitis B virus (HBV) rarely eliminate chronic infection with the virus. High mortality resulting from complicating cirrhosis and hepatocellular carcinoma makes improving anti-HBV therapy an important priority. Recent advances with using gene therapy to counter HBV have potential and are the focus of this review. The stable replication-competent HBV intermediate comprising covalently closed circular DNA (cccDNA) is the template for expression of all viral genes. Inactivating cccDNA has thus been a focus of research aimed at achieving cure for HBV infection. Many studies have reported profound inhibition of replication of the virus using silencing and editing techniques. Therapeutic gene silencing with synthetic short interfering RNA is now in clinical trials. Ability to mutate and permanently inactivate cccDNA with engineered gene editors, such as those derived from CRISPR/Cas or TALENs, is particularly appealing but has not yet reached clinical evaluation. Gene silencing and gene editing potentially provide the means to cure HBV infection. However, achieving efficient delivery of therapeutic sequences, ensuring their specificity of action and progress with other antiviral strategies are likely to determine utility of gene therapy for chronic HBV infection.
Identifiants
pubmed: 32141890
doi: 10.1097/COH.0000000000000623
pii: 01222929-202005000-00009
doi:
Substances chimiques
DNA, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
200-207Références
World Health Organization. Global health sector strategy on viral hepatitis 2016–2021 towards ending viral hepatitis. 2016; Geneva: World Health Organization, Available from: https://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/ Accessed 25 February 2020.
Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: from discovery to regulatory approval. Hepatology 2017; 66:1296–1313.
Revill PA, Chisari FV, Block JM, et al. A global scientific strategy to cure hepatitis B. Lancet Gastroenterol Hepatol 2019; 4:545–558.
Schulze A, Gripon P, Urban S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology 2007; 46:1759–1768.
Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife 2012; 1:e00049.
Koniger C, Wingert I, Marsmann M, et al. Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses. Proc Natl Acad Sci U S A 2014; 111:E4244–E4253.
Kitamura K, Que L, Shimadu M, et al. Flap endonuclease 1 is involved in cccDNA formation in the hepatitis B virus. PLoS Pathog 2018; 14:e1007124.
Lamontagne RJ, Bagga S, Bouchard MJ. Hepatitis B virus molecular biology and pathogenesis. Hepatoma Res 2016; 2:163–186.
Xia Y, Liang TJ. Development of direct-acting antiviral and host-targeting agents for treatment of hepatitis B virus infection. Gastroenterology 2019; 156:311–324.
Loglio A, Ferenci P, Uceda Renteria SC, et al. Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48weeks in HDV-related compensated cirrhosis: a case report of 3 patients. J Hepatol 2019; 71:834–839.
Ahn SH, Kim W, Jung YK, et al. Efficacy and safety of besifovir dipivoxil maleate compared with tenofovir disoproxil fumarate in treatment of chronic hepatitis B virus infection. Clin Gastroenterol Hepatol 2019; 17:1850–1859.e4.
Fukano K, Tsukuda S, Watashi K, Wakita T. Concept of viral inhibitors via NTCP. Semin Liver Dis 2019; 39:78–85.
Yang L, Liu F, Tong X, et al. Treatment of chronic hepatitis B virus infection using small molecule modulators of nucleocapsid assembly: recent advances and perspectives. ACS Infect Dis 2019; 5:713–724.
Bloom K, Maepa MB, Ely A, Arbuthnot P. Gene therapy for chronic HBV-can we eliminate cccDNA? Genes 2018; 9:E207.
Dong J, Ying J, Qiu X, et al. Advanced strategies for eliminating the cccDNA of HBV. Dig Dis Sci 2018; 63:7–15.
EASL. Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017; 67:370–398.
Wang J, Shen T, Huang X, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J Hepatol 2016; 65:700–710.
Giersch K, Allweiss L, Volz T, et al. Serum HBV pgRNA as a clinical marker for cccDNA activity. J Hepatol 2017; 66:460–462.
Wang J, Yu Y, Li G, et al. Relationship between serum HBV-RNA levels and intrahepatic viral as well as histologic activity markers in entecavir-treated patients. J Hepatol 2017; 68:16–24.
van Bommel F, Bartens A, Mysickova A, et al. Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors. Hepatology 2015; 61:66–76.
Luo H, Zhang XX, Cao LH, et al. Serum hepatitis B virus RNA is a predictor of HBeAg seroconversion and virological response with entecavir treatment in chronic hepatitis B patients. World J Gastroenterol 2019; 25:719–728.
Jia W, Zhu MQ, Qi X, et al. Serum hepatitis B virus RNA levels as a predictor of HBeAg seroconversion during treatment with peginterferon alfa-2a. Virol J 2019; 16:61.
Wong DK, Seto WK, Cheung KS, et al. Hepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA. Liver Int 2017; 37:995–1001.
Chen EQ, Feng S, Wang ML, et al. Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B. Sci Rep 2017; 7:173.
Kimura T, Rokuhara A, Sakamoto Y, et al. Sensitive enzyme immunoassay for hepatitis B virus core-related antigens and their correlation to virus load. J Clin Microbiol 2002; 40:439–445.
Mak LY, Wong DK, Cheung KS, et al. Review article: hepatitis B core-related antigen (HBcrAg): an emerging marker for chronic hepatitis B virus infection. Aliment Pharmacol Ther 2018; 47:43–54.
Chen EQ, Wang ML, Tao YC, et al. Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA. J Viral Hepat 2019; 26:586–595.
Testoni B, Lebosse F, Scholtes C, et al. Serum hepatitis B core-related antigen (HBcrAg) correlates with covalently closed circular DNA transcriptional activity in chronic hepatitis B patients. J Hepatol 2019; 70:615–625.
Razin SV, Borunova VV, Maksimenko OG, Kantidze OL. Cys2His2 zinc finger protein family: classification, functions, and major members. Biochemistry 2012; 77:217–226.
Doyon Y, Vo TD, Mendel MC, et al. Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nat Methods 2011; 8:74–79.
Cradick TJ, Keck K, Bradshaw S, et al. Zinc-finger nucleases as a novel therapeutic strategy for targeting hepatitis B virus DNAs. Mol Ther 2010; 18:947–954.
Weber ND, Stone D, Sedlak RH, et al. AAV-mediated delivery of zinc finger nucleases targeting hepatitis B virus inhibits active replication. PLoS One 2014; 9:e97579.
Cermak T, Doyle EL, Christian M, et al. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res 2011; 39:e82.
Boch J, Scholze H, Schornack S, et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 2009; 326:1509–1512.
Bloom K, Ely A, Mussolino C, et al. Inactivation of hepatitis B virus replication in cultured cells and in vivo with engineered transcription activator-like effector nucleases. Mol Ther 2013; 21:1889–1897.
Chen J, Zhang W, Lin J, et al. An efficient antiviral strategy for targeting hepatitis B virus genome using transcription activator-like effector nucleases. Mol Ther 2014; 22:303–311.
Schiwon M, Ehrke-Schulz E, Oswald A, et al. One-vector system for multiplexed CRISPR/Cas9 against hepatitis B virus cccDNA utilizing high-capacity adenoviral vectors. Mol Ther Nucleic Acids 2018; 12:242–253.
Jinek M, Chylinski K, Fonfara I, et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012; 1225829.
Mali P, Yang L, Esvelt KM, et al. RNA-guided human genome engineering via Cas9. Science 2013; 339:823–826.
Lin S-R, Yang H-C, Kuo Y-T, et al. The CRISPR/Cas9 system facilitates clearance of the intrahepatic HBV templates in vivo. Mol Ther Nucleic Acids 2014; 3:e186.
Seeger C, Sohn JA. Targeting hepatitis B virus with CRISPR/Cas9. Mol Ther Nucleic Acids 2014; 3:e216.
Liu X, Hao R, Chen S, et al. Inhibition of hepatitis B virus by the CRISPR/Cas9 system via targeting the conserved regions of the viral genome. J Gen Virol 2015; 96:2252–2261.
Song J, Zhang X, Ge Q, et al. CRISPR/Cas9-mediated knockout of HBsAg inhibits proliferation and tumorigenicity of HBV-positive hepatocellular carcinoma cells. J Cell Biochem 2018; 119:8419–8431.
Scott T, Moyo B, Nicholson S, et al. ssAAVs containing cassettes encoding SaCas9 and guides targeting hepatitis B virus inactivate replication of the virus in cultured cells. Sci Rep 2017; 7:7401.
Liu Y, Zhao M, Gong M, et al. Inhibition of hepatitis B virus replication via HBV DNA cleavage by Cas9 from Staphylococcus aureus. Antiviral Res 2018; 152:58–67.
Li H, Sheng C, Liu H, et al. Inhibition of HBV expression in HBV transgenic mice using AAV-delivered CRISPR-SaCas9. Front Immunol 2018; 9:2080.
Charlesworth CT, Deshpande PS, Dever DP, et al. Identification of preexisting adaptive immunity to Cas9 proteins in humans. Nat Med 2019; 25:249–254.
Wagner DL, Amini L, Wendering DJ, et al. High prevalence of Streptococcus pyogenes Cas9-reactive T cells within the adult human population. Nat Med 2019; 25:242–248.
Karimova M, Beschorner N, Dammermann W, et al. CRISPR/Cas9 nickase-mediated disruption of hepatitis B virus open reading frame S and X. Sci Rep 2015; 5:13734.
Cong L, Ran FA, Cox D, et al. Multiplex genome engineering using CRISPR/Cas systems. Science 2013; 339:819–823.
Ran FA, Hsu PD, Lin CY, et al. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 2013; 154:1380–1389.
Urrutia R. KRAB-containing zinc-finger repressor proteins. Genome Biol 2003; 4:231.
Bloom K, Kaldine H, Cathomen T, et al. Inhibition of replication of hepatitis B virus using transcriptional repressors that target the viral DNA. BMC Infect Dis 2019; 19:802.
Yeo NC, Chavez A, Lance-Byrne A, et al. An enhanced CRISPR repressor for targeted mammalian gene regulation. Nat Methods 2018; 15:611–616.
Thakore PI, Kwon JB, Nelson CE, et al. RNA-guided transcriptional silencing in vivo with S. aureus CRISPR-Cas9 repressors. Nat Commun 2018; 9:1674.
Song J, Cano-Rodriquez D, Winkle M, et al. Targeted epigenetic editing of SPDEF reduces mucus production in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 2017; 312:L334–L347.
Mlambo T, Romito M, Cornu TI, Mussolino C. Delivery of designer epigenome modifiers into primary human T cells. Methods Mol Biol 2018; 1767:189–203.
Josipovic G, Zoldos V, Vojta A. Active fusions of Cas9 orthologs. J Biotechnol 2019; 301:18–23.
Zhu LJ, Lawrence M, Gupta A, et al. GUIDEseq: a bioconductor package to analyze GUIDE-Seq datasets for CRISPR-Cas nucleases. BMC Genomics 2017; 18:379.
Tsai SQ, Nguyen NT, Malagon-Lopez J, et al. CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets. Nat Methods 2017; 14:607–614.
Wienert B, Wyman SK, Richardson CD, et al. Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq. Science 2019; 364:286–289.
Kostyushev D, Brezgin S, Kostyusheva A, et al. Orthologous CRISPR/Cas9 systems for specific and efficient degradation of covalently closed circular DNA of hepatitis B virus. Cell Mol Life Sci 2019; 76:1779–1794.
Muller M, Lee CM, Gasiunas G, et al. Streptococcus thermophilus CRISPR-Cas9 systems enable specific editing of the human genome. Mol Ther 2016; 24:636–644.
Jo DH, Koo T, Cho CS, et al. Long-term effects of in vivo genome editing in the mouse retina using Campylobacter jejuni Cas9 expressed via adeno-associated virus. Mol Ther 2019; 27:130–136.
Kim E, Koo T, Park SW, et al. In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni. Nat Commun 2017; 8:14500.
Anzalone AV, Randolph PB, Davis JR, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 2019; 576:149–157.
Levanova A, Poranen MM. RNA interference as a prospective tool for the control of human viral infections. Front Microbiol 2018; 9:2151.
Qureshi A, Tantray VG, Kirmani AR, Ahangar AG. A review on current status of antiviral siRNA. Rev Med Virol 2018; 28:e1976.
Guerrieri F, Belloni L, D’Andrea D, et al. Genome-wide identification of direct HBx genomic targets. BMC Genomics 2017; 18:184.
Decorsiere A, Mueller H, van Breugel PC, et al. Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature 2016; 531:386–389.
Maepa MB, Ely A, Grayson W, Arbuthnot P. Sustained inhibition of HBV replication in vivo after systemic injection of AAVs encoding artificial antiviral primary microRNAs. Mol Ther Nucleic Acids 2017; 7:190–199.
Stanford S, Pink R, Creagh D, et al. Adenovirus-associated antibodies in UK cohort of hemophilia patients: a seroprevalence study of the presence of adenovirus-associated virus vector-serotypes AAV5 and AAV8 neutralizing activity and antibodies in patients with hemophilia A. Res Pract Thromb Haemost 2019; 3:261–267.
Calcedo R, Vandenberghe LH, Gao G, et al. Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis 2009; 199:381–390.
Kruzik A, Fetahagic D, Hartlieb B, et al. Prevalence of anti-adeno-associated virus immune responses in international cohorts of healthy donors. Mol Ther Methods Clin Dev 2019; 14:126–133.
Manno CS, Pierce GF, Arruda VR, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med 2006; 12:342–347.
Mingozzi F, Maus MV, Hui DJ, et al. CD8(+) T-cell responses to adeno-associated virus capsid in humans. Nat Med 2007; 13:419–422.
Mingozzi F, Meulenberg JJ, Hui DJ, et al. AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells. Blood 2009; 114:2077–2086.
Paulk NK, Pekrun K, Zhu E, et al. Bioengineered AAV capsids with combined high human liver transduction in vivo and unique humoral seroreactivity. Mol Ther 2018; 26:289–303.
Kobayashi Y, Shimazu T, Murata K, et al. An endogenous adeno-associated virus element in elephants. Virus Res 2019; 262:10–14.
Santiago-Ortiz J, Ojala DS, Westesson O, et al. AAV ancestral reconstruction library enables selection of broadly infectious viral variants. Gene Ther 2015; 22:934–946.
Zinn E, Pacouret S, Khaychuk V, et al. In silico reconstruction of the viral evolutionary lineage yields a potent gene therapy vector. Cell Rep 2015; 12:1056–1068.
Wang J, Chen R, Zhang R, et al. The gRNA-miRNA-gRNA ternary cassette combining CRISPR/Cas9 with RNAi approach strongly inhibits hepatitis B virus replication. Theranostics 2017; 7:3090–3105.
Kostyusheva AP, Kostyushev DS, Brezgin SA, et al. Small Molecular Inhibitors of DNA double strand break repair pathways increase the anti-HBV activity of CRISPR/Cas9. Mol Biol 2019; 53:311–323.