Progress and Prospects of Anti-HBV Gene Therapy Development

Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous...

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Published inInternational journal of molecular sciences Vol. 16; no. 8; pp. 17589 - 17610
Main Authors Maepa, Mohube, Roelofse, Ilke, Ely, Abdullah, Arbuthnot, Patrick
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 31.07.2015
MDPI
Subjects
DNA, Viral - antagonists & inhibitors
DNA, Viral - genetics
Gene therapy
Genetic Therapy
Hepatitis
Hepatitis B virus
Hepatitis B virus - genetics
Hepatitis B virus - pathogenicity
Hepatitis B, Chronic - genetics
Hepatitis B, Chronic - therapy
Hepatitis B, Chronic - virology
Humans
Oligonucleotides, Antisense - therapeutic use
Review
Ribonucleic acid
RNA
RNA Editing - genetics
RNA Interference
RNA, Catalytic - genetics
RNA, Catalytic - therapeutic use
Vaccines
Virus Replication - genetics
gene therapy
ribozymes
RNAi
HBV
gene editing
antisense oligonucleotides
Online AccessGet full text
ISSN1422-0067
1661-6596
1422-0067
DOI10.3390/ijms160817589

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Abstract Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous research on developing better drugs against chronic HBV infection. Advances in understanding the life cycle of HBV and improvements in gene-disabling technologies have been impressive. This has led to development of better HBV infection models and discovery of new drug candidates. Ideally, a regimen against chronic HBV infection should completely eliminate all viral replicative intermediates, especially covalently closed circular DNA (cccDNA). For the past few decades, nucleic acid-based therapy has emerged as an attractive alternative that may result in complete clearance of HBV in infected patients. Several genetic anti-HBV strategies have been developed. The most studied approaches include the use of antisense oligonucleotides, ribozymes, RNA interference effectors and gene editing tools. This review will summarize recent developments and progress made in the use of gene therapy against HBV.
AbstractList Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous research on developing better drugs against chronic HBV infection. Advances in understanding the life cycle of HBV and improvements in gene-disabling technologies have been impressive. This has led to development of better HBV infection models and discovery of new drug candidates. Ideally, a regimen against chronic HBV infection should completely eliminate all viral replicative intermediates, especially covalently closed circular DNA (cccDNA). For the past few decades, nucleic acid-based therapy has emerged as an attractive alternative that may result in complete clearance of HBV in infected patients. Several genetic anti-HBV strategies have been developed. The most studied approaches include the use of antisense oligonucleotides, ribozymes, RNA interference effectors and gene editing tools. This review will summarize recent developments and progress made in the use of gene therapy against HBV.
Author Ely, Abdullah
Maepa, Mohube
Roelofse, Ilke
Arbuthnot, Patrick
AuthorAffiliation Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Health Sciences Faculty, University of the Witwatersrand, Wits 2050, South Africa; E-Mails: Betty.Maepa@wits.ac.za (M.B.M.); Ilke.Roelofse@wits.ac.za (I.R.); Abdullah.Ely@wits.ac.za (A.E.)
AuthorAffiliation_xml – name: Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Health Sciences Faculty, University of the Witwatersrand, Wits 2050, South Africa; E-Mails: Betty.Maepa@wits.ac.za (M.B.M.); Ilke.Roelofse@wits.ac.za (I.R.); Abdullah.Ely@wits.ac.za (A.E.)
Author_xml – sequence: 1
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  givenname: Abdullah
  surname: Ely
  fullname: Ely, Abdullah
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  givenname: Patrick
  surname: Arbuthnot
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Cites_doi 10.1002/ijc.28704
10.2174/1566524043360410
10.1038/nm.3793
10.3390/v6062376
10.1111/j.1478-3231.2004.0966.x
10.1186/s12977-015-0150-z
10.1016/S0140-6736(11)60756-3
10.1038/nature04791
10.1101/gr.099747.109
10.4254/wjh.v4.i3.74
10.1172/JCI72992
10.1006/jmbi.2000.3560
10.1155/2014/718743
10.1038/nbt.3198
10.1371/journal.pgen.1000869
10.1006/bbrc.2000.2209
10.1073/pnas.0801775105
10.1126/science.1178811
10.1016/j.tibtech.2013.04.004
10.1111/hepr.12189
10.1073/pnas.89.13.5710
10.1038/nature07845
10.1089/oli.2006.0049
10.1007/s11095-011-0554-y
10.1002/dvg.22422
10.1038/sj.gt.3300441
10.1038/mt.2013.212
10.1016/j.ejphar.2013.09.050
10.1093/nar/gkp446
10.1021/bc025559y
10.1093/hmg/ddu349
10.1016/j.ymthe.2005.06.094
10.1111/jgh.12718
10.1016/j.jhep.2015.01.020
10.4254/wjh.v7.i2.150
10.1016/j.cca.2005.11.023
10.1002/j.1460-2075.1993.tb05767.x
10.1128/AAC.46.9.3057-3060.2002
10.1016/j.bmcl.2014.07.032
10.1002/cbic.201402551
10.1371/journal.pone.0097579
10.1016/j.antiviral.2007.06.014
10.7554/eLife.00049
10.1016/j.febslet.2005.08.079
10.1038/mtna.2014.38
10.1177/1087057112463066
10.1016/S0021-9258(18)42295-8
10.1038/nbt.3190
10.1186/1743-422X-7-61
10.1515/BC.2001.077
10.1038/nbt0605-686
10.1128/MCB.00487-06
10.1002/hep.21896
10.1038/mt.2013.170
10.1007/s12041-010-0073-3
10.1016/j.mib.2014.02.007
10.1038/nrg2842
10.1146/annurev.biophys.30.1.457
10.1002/hep.510230601
10.1021/jm9013295
10.1093/pcp/pcu170
10.1021/bi500602z
10.3748/wjg.v6.i3.377
10.1038/mt.2013.31
10.1016/j.cell.2014.05.010
10.1128/JVI.03533-12
10.3390/ijms15022892
10.1002/rmv.705
10.1007/s10126-014-9587-7
10.1093/jac/dkg163
10.1101/gr.129635.111
10.3748/wjg.v8.i1.91
10.1093/nar/gkt754
10.1099/0022-1317-71-12-3021
10.1007/s10529-014-1690-3
10.1002/bit.24890
10.1111/j.1365-2893.2005.00612.x
10.1038/nrm3486
10.1016/j.bbrc.2014.02.099
10.1016/j.virusres.2005.06.005
10.1172/JCI43565
10.1016/j.jconrel.2014.12.036
10.1038/nbt.2842
10.1038/nrg3686
10.1016/j.str.2013.06.013
10.1038/mt.2008.82
10.1111/j.1365-2893.1996.tb00076.x
10.1093/nar/gki155
10.1126/science.1252967
10.1038/mt.2010.20
10.1006/bbrc.1997.6099
10.1111/j.1440-1746.2010.06546.x
10.1089/oli.2011.0280
10.1016/j.tim.2014.01.007
10.1016/j.antiviral.2015.03.015
10.1016/0166-3542(95)00050-V
10.1076/ocii.7.3.189.4007
10.1128/JVI.00366-08
10.1007/978-1-4939-1538-5_10
10.1016/j.ymthe.2003.12.013
10.1101/gr.122879.111
10.1089/108729002320351575
10.2144/97222rr03
10.1128/JVI.01024-14
10.1046/j.1365-2893.2002.00383.x
10.1089/hum.2012.239
10.1038/sj.gt.3301464
10.1038/gt.2014.94
10.1038/mtna.2014.68
10.1146/annurev-biochem-010909-095056
10.1016/j.virol.2014.12.001
10.1128/JVI.03540-12
10.1038/mt.2013.37
10.1016/j.cell.2009.01.002
10.1038/nature03556
10.1007/s12013-014-9847-1
10.1038/gt.2015.2
10.1046/j.1440-1746.2001.02548.x
10.1016/j.tree.2008.06.005
10.1038/35888
10.1038/mt.2008.144
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Issue 8
Keywords gene therapy
ribozymes
RNAi
HBV
gene editing
antisense oligonucleotides
Language English
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References Meenken (ref_39) 1999; 7
Shabalina (ref_70) 2008; 23
Xia (ref_52) 2013; 21
Offensperger (ref_33) 1993; 12
Ely (ref_90) 2009; 37
Sun (ref_116) 2013; 110
Robaczewska (ref_46) 2001; 8
Osakabe (ref_106) 2015; 56
Sebestyen (ref_80) 2015; 1218
ref_133
Passman (ref_55) 2000; 268
Song (ref_53) 2002; 8
Weinberg (ref_66) 2007; 17
Xu (ref_6) 2015; 30
Weber (ref_127) 2014; 9
Dong (ref_131) 2015; 118
Lee (ref_110) 2010; 20
Montuclard (ref_2) 2015; 62
Ding (ref_17) 2011; 21
Qi (ref_132) 2014; 88
Cradick (ref_24) 2010; 18
Grimm (ref_88) 2010; 120
Feng (ref_59) 2001; 16
Sun (ref_43) 2014; 23
Vandenbroucke (ref_30) 2014; 135
Gaj (ref_95) 2013; 31
Urnov (ref_97) 2010; 11
Lamb (ref_118) 2013; 41
Delaney (ref_12) 2002; 46
Yan (ref_14) 2013; 87
Nash (ref_56) 2005; 12
Cirak (ref_44) 2011; 378
Kennedy (ref_28) 2015; 476
Feld (ref_11) 2007; 76
Hasselblatt (ref_19) 2005; 33
Zhang (ref_104) 2015; 37
Arbuthnot (ref_3) 2005; 25
Fedor (ref_49) 2000; 297
Bagheri (ref_51) 2004; 4
Yang (ref_13) 2014; 24
Katen (ref_10) 2013; 21
Li (ref_61) 2005; 114
Fineran (ref_125) 2014; 18
Yao (ref_34) 1996; 3
Hsu (ref_122) 2014; 157
Grimm (ref_86) 2006; 441
Ely (ref_91) 2008; 16
Li (ref_23) 2014; 69
Lin (ref_129) 2014; 3
Ruiz (ref_67) 1997; 22
ref_83
Sripathy (ref_121) 2006; 26
ref_82
Zhang (ref_45) 2006; 41
ref_81
Prakash (ref_41) 2010; 53
Groner (ref_120) 2010; 6
Zhao (ref_22) 2013; 18
ref_85
Doherty (ref_21) 2001; 30
ref_84
Alwin (ref_103) 2005; 12
Karayiannis (ref_5) 2003; 51
Nakazono (ref_38) 1996; 23
Schulze (ref_8) 2007; 46
Sander (ref_123) 2014; 32
Pan (ref_60) 2004; 9
Cox (ref_101) 2015; 21
Urnov (ref_114) 2005; 435
Franco (ref_1) 2012; 4
Wen (ref_62) 2000; 6
Gupta (ref_98) 2014; 124
Kim (ref_96) 2014; 15
Xu (ref_76) 2015; 54
Deng (ref_36) 2009; 17
Wang (ref_112) 2012; 22
Yan (ref_9) 2012; 1
Kew (ref_126) 2011; 26
Zhen (ref_29) 2015; 22
Maruyama (ref_100) 2015; 33
Wu (ref_25) 2014; 446
Hammond (ref_69) 2005; 579
Fire (ref_71) 1998; 391
Yuan (ref_134) 2007; 38
Yao (ref_35) 1996; 40
Kong (ref_78) 2012; 29
Joung (ref_117) 2013; 14
Sioud (ref_64) 1997; 231
Huang (ref_77) 2014; 44
McBride (ref_89) 2008; 105
Davidson (ref_124) 2014; 22
Bloom (ref_26) 2013; 21
Haussecker (ref_73) 2015; 347
Gebbing (ref_7) 2015; 7
Tan (ref_63) 2002; 12
Ivacik (ref_4) 2011; 21
Wooddell (ref_79) 2013; 21
Bartel (ref_68) 2009; 136
Khan (ref_20) 2006; 367
Goodarzi (ref_31) 1990; 71 Pt 12
Ketting (ref_18) 2011; 700
Wu (ref_32) 1992; 267
Menke (ref_108) 2013; 51
Guan (ref_107) 2014; 16
Wu (ref_47) 2001; 42
Yang (ref_50) 2014; 6
Townsend (ref_105) 2009; 459
Seeger (ref_130) 2014; 3
Korba (ref_37) 1995; 28
Feng (ref_58) 2001; 382
Chu (ref_99) 2015; 33
Jensen (ref_40) 2002; 13
Ivacik (ref_92) 2015; 22
Ain (ref_119) 2015; 205
Boch (ref_115) 2009; 326
Welch (ref_54) 1997; 4
Sun (ref_87) 2013; 24
Morrissey (ref_57) 2002; 9
Lee (ref_111) 2012; 22
Deng (ref_42) 2013; 30
Chen (ref_128) 2014; 22
Zhong (ref_15) 2013; 87
Zhu (ref_27) 2015; 12
Watashi (ref_16) 2014; 15
Chen (ref_74) 2013; 721
McCall (ref_65) 1992; 89
Mowa (ref_93) 2014; 2014
Giering (ref_94) 2008; 16
Valenzuela (ref_75) 2015; 16
Klug (ref_102) 2010; 79
Kandavelou (ref_113) 2005; 23
Angaji (ref_72) 2010; 89
Zimmerman (ref_109) 2008; 82
Wang (ref_48) 2010; 7
25137139 - Mol Ther Nucleic Acids. 2014 Aug 19;3:e186
23481322 - Mol Ther. 2013 May;21(5):995-1003
23042077 - J Biomol Screen. 2013 Apr;18(4):378-87
16426595 - Clin Chim Acta. 2006 May;367(1-2):20-7
21466387 - Oligonucleotides. 2011 Mar-Apr;21(2):77-84
25798939 - Nat Biotechnol. 2015 May;33(5):538-42
23829557 - Hum Gene Ther. 2013 Aug;24(8):739-50
24025750 - Mol Ther. 2014 Feb;22(2):303-11
24099962 - Eur J Pharmacol. 2013 Dec 5;721(1-3):86-95
8675142 - Hepatology. 1996 Jun;23(6):1297-303
20192761 - Annu Rev Biochem. 2010;79:213-31
24582529 - Trends Microbiol. 2014 Apr;22(4):218-25
25338920 - Gene Ther. 2015 Feb;22(2):163-71
8458338 - EMBO J. 1993 Mar;12(3):1257-62
10715200 - J Mol Biol. 2000 Mar 24;297(2):269-91
25097139 - Mar Biotechnol (NY). 2014 Dec;16(6):739-47
24906146 - Cell. 2014 Jun 5;157(6):1262-78
24637219 - Curr Opin Microbiol. 2014 Apr;18:83-9
15698393 - Liver Int. 2005 Feb;25(1):9-15
21755468 - Adv Exp Med Biol. 2011;700:1-14
25553515 - Virology. 2015 Feb;476:196-205
25553825 - J Control Release. 2015 May 10;205:120-7
11423935 - Gene Ther. 2001 Jun;8(11):874-81
15806097 - Nature. 2005 Jun 2;435(7042):646-51
18046710 - Hepatology. 2007 Dec;46(6):1759-68
16054262 - Virus Res. 2005 Dec;114(1-2):126-32
12183271 - Antimicrob Agents Chemother. 2002 Sep;46(9):3057-60
23169466 - Nat Rev Mol Cell Biol. 2013 Jan;14(1):49-55
24690881 - Nat Rev Genet. 2014 May;15(5):321-34
8629815 - Antiviral Res. 1995 Nov;28(3):225-42
21199526 - J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:144-52
19933107 - Science. 2009 Dec 11;326(5959):1509-12
8886096 - Acta Virol. 1996 Feb;40(1):35-9
23871485 - Structure. 2013 Aug 6;21(8):1406-16
25416289 - Plant Cell Physiol. 2015 Mar;56(3):389-400
19404258 - Nature. 2009 May 21;459(7245):442-5
25654603 - Nat Med. 2015 Feb;21(2):121-31
23664777 - Trends Biotechnol. 2013 Jul;31(7):397-405
25808449 - Retrovirology. 2015;12:22
17262957 - Yao Xue Xue Bao. 2006 Nov;41(11):1111-5
16039907 - Mol Ther. 2005 Oct;12(4):610-7
11833079 - World J Gastroenterol. 2002 Feb;8(1):91-4
12654750 - J Antimicrob Chemother. 2003 Apr;51(4):761-85
20236514 - Virol J. 2010;7:61
20221260 - PLoS Genet. 2010 Mar;6(3):e1000869
16724069 - Nature. 2006 May 25;441(7092):537-41
23508559 - Biotechnol Bioeng. 2013 Jul;110(7):1811-21
21273705 - J Genet. 2010 Dec;89(4):527-37
2177093 - J Gen Virol. 1990 Dec;71 ( Pt 12):3021-5
20108935 - J Med Chem. 2010 Feb 25;53(4):1636-50
25487859 - Chembiochem. 2015 Jan 19;16(2):262-7
24569930 - Cell Biochem Biophys. 2014 Jul;69(3):649-54
11471200 - Croat Med J. 2001 Aug;42(4):463-6
12431202 - J Viral Hepat. 2002 Nov;9(6):411-8
9282175 - Gene Ther. 1997 Jul;4(7):736-43
24059065 - Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2013 Aug;30(4):828-32, 837
25280729 - Biotechnol Lett. 2015 Feb;37(2):299-305
11405228 - Biol Chem. 2001 Apr;382(4):655-60
20038330 - Zhonghua Gan Zang Bing Za Zhi. 2009 Dec;17(12):900-4
20717154 - Nat Rev Genet. 2010 Sep;11(9):636-46
17441333 - Sichuan Da Xue Xue Bao Yi Xue Ban. 2007 Mar;38(2):217-21
23913666 - Genesis. 2013 Sep;51(9):605-18
25635512 - Biochemistry. 2015 Feb 10;54(5):1268-77
24932966 - Viruses. 2014 Jun;6(6):2376-91
9043708 - Biotechniques. 1997 Feb;22(2):338-45
17709147 - Antiviral Res. 2007 Nov;76(2):168-77
24827459 - PLoS One. 2014;9(5):e97579
18715673 - Trends Ecol Evol. 2008 Oct;23(10):578-87
18398004 - Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5868-73
15267221 - Curr Mol Med. 2004 Aug;4(5):489-506
21784508 - Lancet. 2011 Aug 13;378(9791):595-605
25625233 - J Hepatol. 2015 Jun;62(6):1265-71
25003129 - Biomed Res Int. 2014;2014:718743
15640448 - Nucleic Acids Res. 2005;33(1):114-25
17461767 - Oligonucleotides. 2007 Spring;17(1):104-12
25803306 - Nat Biotechnol. 2015 May;33(5):543-8
25745148 - Science. 2015 Mar 6;347(6226):1069-70
23439496 - Mol Ther. 2013 May;21(5):973-85
12238814 - Antisense Nucleic Acid Drug Dev. 2002 Aug;12(4):257-64
24584096 - Nat Biotechnol. 2014 Apr;32(4):347-55
25127104 - Bioorg Med Chem Lett. 2014 Sep 1;24(17):4247-9
15985004 - J Viral Hepat. 2005 Jul;12(4):346-56
24557582 - Int J Mol Sci. 2014;15(2):2892-905
18665161 - Mol Ther. 2008 Sep;16(9):1630-6
1631050 - Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5710-4
25319651 - Methods Mol Biol. 2015;1218:163-86
25729471 - World J Hepatol. 2015 Feb 27;7(2):150-64
22183967 - Genome Res. 2012 Mar;22(3):539-48
25514649 - Mol Ther Nucleic Acids. 2014 Dec 16;3:e216
24807718 - J Virol. 2014 Jul;88(14):8045-56
25652100 - Gene Ther. 2015 May;22(5):404-12
19952142 - Genome Res. 2010 Jan;20(1):81-9
21913277 - Rev Med Virol. 2011 Nov;21(6):383-96
25035419 - Hum Mol Genet. 2014 Dec 1;23(23):6302-17
20160705 - Mol Ther. 2010 May;18(5):947-54
15093190 - Mol Ther. 2004 Apr;9(4):596-606
8736236 - J Viral Hepat. 1996 Jan;3(1):19-22
25843425 - Antiviral Res. 2015 Jun;118:110-7
11686839 - J Gastroenterol Hepatol. 2001 Oct;16(10):1125-30
25271723 - J Clin Invest. 2014 Oct;124(10):4154-61
16954381 - Mol Cell Biol. 2006 Nov;26(22):8623-38
23799901 - Hepatol Res. 2014 Aug;44(8):897-906
22489259 - World J Hepatol. 2012 Mar 27;4(3):74-80
16214139 - FEBS Lett. 2005 Oct 31;579(26):5822-9
18431360 - Mol Ther. 2008 Jun;16(6):1105-12
21842305 - Pharm Res. 2012 Feb;29(2):362-74
9486653 - Nature. 1998 Feb 19;391(6669):806-11
23150796 - Elife. 2012;1:e00049
19474340 - Nucleic Acids Res. 2009 Jul;37(13):e91
23596296 - J Virol. 2013 Jun;87(12):7176-84
23678176 - J Virol. 2013 Jul;87(14):7977-91
1618751 - J Biol Chem. 1992 Jun 25;267(18):12436-9
19167326 - Cell. 2009 Jan 23;136(2):215-33
10611727 - Ocul Immunol Inflamm. 1999 Dec;7(3-4):189-98
22434427 - Genome Res. 2012 Jul;22(7):1316-26
24382818 - Int J Cancer. 2014 Aug 1;135(3):742-50
18524822 - J Virol. 2008 Aug;82(16):8013-21
20697157 - J Clin Invest. 2010 Sep;120(9):3106-19
11441810 - Annu Rev Biophys Biomol Struct. 2001;30:457-75
10679273 - Biochem Biophys Res Commun. 2000 Feb 24;268(3):728-33
11819602 - World J Gastroenterol. 2000 Jun;6(3):377-380
24589733 - Biochem Biophys Res Commun. 2014 Mar 28;446(1):261-6
25167956 - J Gastroenterol Hepatol. 2015 Feb;30(2):372-8
9070287 - Biochem Biophys Res Commun. 1997 Feb 13;231(2):397-402
15940239 - Nat Biotechnol. 2005 Jun;23(6):686-7
23883864 - Mol Ther. 2013 Oct;21(10):1889-97
12236779 - Bioconjug Chem. 2002 Sep-Oct;13(5):975-84
23980031 - Nucleic Acids Res. 2013 Nov;41(21):9779-85
References_xml – volume: 135
  start-page: 742
  year: 2014
  ident: ref_30
  article-title: Antisense oligonucleotides against TNFR1 prevent toxicity of TNF/IFNγ treatment in mouse tumor models
  publication-title: Int. J. Cancer
  doi: 10.1002/ijc.28704
– volume: 4
  start-page: 489
  year: 2004
  ident: ref_51
  article-title: Ribozymes in the age of molecular therapeutics
  publication-title: Curr. Mol. Med.
  doi: 10.2174/1566524043360410
– volume: 21
  start-page: 121
  year: 2015
  ident: ref_101
  article-title: Therapeutic genome editing: Prospects and challenges
  publication-title: Nat. Med.
  doi: 10.1038/nm.3793
– volume: 6
  start-page: 2376
  year: 2014
  ident: ref_50
  article-title: Engineered RNase P ribozymes effectively inhibit human cytomegalovirus gene expression and replication
  publication-title: Viruses
  doi: 10.3390/v6062376
– volume: 25
  start-page: 9
  year: 2005
  ident: ref_3
  article-title: Exploiting the RNA interference pathway to counter hepatitis B virus replication
  publication-title: Liver Int.
  doi: 10.1111/j.1478-3231.2004.0966.x
– volume: 12
  start-page: 22
  year: 2015
  ident: ref_27
  article-title: The CRISPR-cas9 system inactivates latent HIV-1 proviral DNA
  publication-title: Retrovirology
  doi: 10.1186/s12977-015-0150-z
– volume: 378
  start-page: 595
  year: 2011
  ident: ref_44
  article-title: Exon skipping and dystrophin restoration in patients with duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: An open-label, phase 2, dose-escalation study
  publication-title: Lancet
  doi: 10.1016/S0140-6736(11)60756-3
– volume: 441
  start-page: 537
  year: 2006
  ident: ref_86
  article-title: Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways
  publication-title: Nature
  doi: 10.1038/nature04791
– volume: 20
  start-page: 81
  year: 2010
  ident: ref_110
  article-title: Targeted chromosomal deletions in human cells using zinc finger nucleases
  publication-title: Genome Res.
  doi: 10.1101/gr.099747.109
– volume: 4
  start-page: 74
  year: 2012
  ident: ref_1
  article-title: Hepatitis B: Epidemiology and prevention in developing countries
  publication-title: World J. Hepatol.
  doi: 10.4254/wjh.v4.i3.74
– volume: 124
  start-page: 4154
  year: 2014
  ident: ref_98
  article-title: Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9
  publication-title: J. Clin. Investig.
  doi: 10.1172/JCI72992
– volume: 297
  start-page: 269
  year: 2000
  ident: ref_49
  article-title: Structure and function of the hairpin ribozyme
  publication-title: J. Mol. Biol.
  doi: 10.1006/jmbi.2000.3560
– volume: 2014
  start-page: 718743
  year: 2014
  ident: ref_93
  article-title: Inhibition of hepatitis B virus replication by helper dependent adenoviral vectors expressing artificial anti-HBV pri-miRs from a liver-specific promoter
  publication-title: Biomed. Res. Int.
  doi: 10.1155/2014/718743
– volume: 33
  start-page: 543
  year: 2015
  ident: ref_99
  article-title: Increasing the efficiency of homology-directed repair for CRISPR-Cas9-induced precise gene editing in mammalian cells
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.3198
– volume: 6
  start-page: e1000869
  year: 2010
  ident: ref_120
  article-title: KRAB-zinc finger proteins and KAP1 can mediate long-range transcriptional repression through heterochromatin spreading
  publication-title: PLoS Genet.
  doi: 10.1371/journal.pgen.1000869
– volume: 268
  start-page: 728
  year: 2000
  ident: ref_55
  article-title: In situ demonstration of inhibitory effects of hammerhead ribozymes that are targeted to the hepatitis Bx sequence in cultured cells
  publication-title: Biochem. Biophys. Res. Commun.
  doi: 10.1006/bbrc.2000.2209
– volume: 105
  start-page: 5868
  year: 2008
  ident: ref_89
  article-title: Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: Implications for the therapeutic development of RNAi
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.0801775105
– volume: 326
  start-page: 1509
  year: 2009
  ident: ref_115
  article-title: Breaking the code of DNA binding specificity of TAL-type III effectors
  publication-title: Science
  doi: 10.1126/science.1178811
– volume: 31
  start-page: 397
  year: 2013
  ident: ref_95
  article-title: ZFN, TALEN, and CRISPR-cas-based methods for genome engineering
  publication-title: Trends Biotechnol.
  doi: 10.1016/j.tibtech.2013.04.004
– ident: ref_83
– volume: 44
  start-page: 897
  year: 2014
  ident: ref_77
  article-title: Targeted delivery of siRNA against hepatitis B virus by preS1 peptide molecular ligand
  publication-title: Hepatol. Res.
  doi: 10.1111/hepr.12189
– volume: 89
  start-page: 5710
  year: 1992
  ident: ref_65
  article-title: Minimal sequence requirements for ribozyme activity
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.89.13.5710
– volume: 459
  start-page: 442
  year: 2009
  ident: ref_105
  article-title: High-frequency modification of plant genes using engineered zinc-finger nucleases
  publication-title: Nature
  doi: 10.1038/nature07845
– volume: 17
  start-page: 900
  year: 2009
  ident: ref_36
  article-title: Inhibition of hepatitis B virus (HBV) replication using antisense LNA targeting to both S and C genes in HBV
  publication-title: Zhonghua Gan Zang Bing Za Zhi
– volume: 17
  start-page: 104
  year: 2007
  ident: ref_66
  article-title: Effective anti-hepatitis B virus hammerhead ribozymes derived from multimeric precursors
  publication-title: Oligonucleotides
  doi: 10.1089/oli.2006.0049
– volume: 29
  start-page: 362
  year: 2012
  ident: ref_78
  article-title: Cationic lipid-coated gold nanoparticles as efficient and non-cytotoxic intracellular siRNA delivery vehicles
  publication-title: Pharm. Res.
  doi: 10.1007/s11095-011-0554-y
– volume: 51
  start-page: 605
  year: 2013
  ident: ref_108
  article-title: Engineering subtle targeted mutations into the mouse genome
  publication-title: Genesis
  doi: 10.1002/dvg.22422
– volume: 4
  start-page: 736
  year: 1997
  ident: ref_54
  article-title: Intracellular application of hairpin ribozyme genes against hepatitis B virus
  publication-title: Gene Ther.
  doi: 10.1038/sj.gt.3300441
– volume: 22
  start-page: 303
  year: 2014
  ident: ref_128
  article-title: An efficient antiviral strategy for targeting hepatitis B virus genome using transcription activator-like effector nucleases
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2013.212
– volume: 721
  start-page: 86
  year: 2013
  ident: ref_74
  article-title: 5′-Triphosphate-siRNA activates RIG-I-dependent type I interferon production and enhances inhibition of hepatitis B virus replication in HepG2.2.15 cells
  publication-title: Eur. J. Pharmacol.
  doi: 10.1016/j.ejphar.2013.09.050
– volume: 37
  start-page: e91
  year: 2009
  ident: ref_90
  article-title: Efficient silencing of gene expression with modular trimeric Pol II expression cassettes comprising microRNA shuttles
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkp446
– volume: 13
  start-page: 975
  year: 2002
  ident: ref_40
  article-title: Antisense oligonucleotides delivered to the lysosome escape and actively inhibit the hepatitis B virus
  publication-title: Bioconjug. Chem.
  doi: 10.1021/bc025559y
– volume: 23
  start-page: 6302
  year: 2014
  ident: ref_43
  article-title: Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity
  publication-title: Hum. Mol. Genet.
  doi: 10.1093/hmg/ddu349
– volume: 12
  start-page: 610
  year: 2005
  ident: ref_103
  article-title: Custom zinc-finger nucleases for use in human cells
  publication-title: Mol. Ther.
  doi: 10.1016/j.ymthe.2005.06.094
– volume: 30
  start-page: 372
  year: 2015
  ident: ref_6
  article-title: Long-term lamivudine treatment achieves regression of advanced liver fibrosis/cirrhosis in patients with chronic hepatitis B
  publication-title: J. Gastroenterol. Hepatol.
  doi: 10.1111/jgh.12718
– volume: 62
  start-page: 1265
  year: 2015
  ident: ref_2
  article-title: Causes of death in people with chronic HBV infection: A population-based cohort study
  publication-title: J. Hepatol.
  doi: 10.1016/j.jhep.2015.01.020
– volume: 7
  start-page: 150
  year: 2015
  ident: ref_7
  article-title: Gene therapeutic approaches to inhibit hepatitis B virus replication
  publication-title: World J. Hepatol.
  doi: 10.4254/wjh.v7.i2.150
– volume: 367
  start-page: 20
  year: 2006
  ident: ref_20
  article-title: Ribozyme: A clinical tool
  publication-title: Clin. Chim. Acta
  doi: 10.1016/j.cca.2005.11.023
– volume: 12
  start-page: 1257
  year: 1993
  ident: ref_33
  article-title: In vivo inhibition of duck hepatitis B virus replication and gene expression by phosphorothioate modified antisense oligodeoxynucleotides
  publication-title: EMBO J.
  doi: 10.1002/j.1460-2075.1993.tb05767.x
– volume: 46
  start-page: 3057
  year: 2002
  ident: ref_12
  article-title: Phenylpropenamide derivatives AT-61 and AT-130 inhibit replication of wild-type and lamivudine-resistant strains of hepatitis B virus in vitro
  publication-title: Antimicrob. Agents Chemother.
  doi: 10.1128/AAC.46.9.3057-3060.2002
– volume: 700
  start-page: 1
  year: 2011
  ident: ref_18
  article-title: MicroRNA biogenesis and function: An overview
  publication-title: Adv. Exp. Med. Biol.
– volume: 24
  start-page: 4247
  year: 2014
  ident: ref_13
  article-title: A new series of HAPs as anti-HBV agents targeting at capsid assembly
  publication-title: Bioorg. Med. Chem. Lett.
  doi: 10.1016/j.bmcl.2014.07.032
– volume: 16
  start-page: 262
  year: 2015
  ident: ref_75
  article-title: Base modification strategies to modulate immune stimulation by an siRNA
  publication-title: ChemBioChem
  doi: 10.1002/cbic.201402551
– volume: 9
  start-page: e97579
  year: 2014
  ident: ref_127
  article-title: AAV-mediated delivery of zinc finger nucleases targeting hepatitis B virus inhibits active replication
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0097579
– volume: 76
  start-page: 168
  year: 2007
  ident: ref_11
  article-title: The phenylpropenamide derivative AT-130 blocks HBV replication at the level of viral RNA packaging
  publication-title: Antivir. Res.
  doi: 10.1016/j.antiviral.2007.06.014
– volume: 1
  start-page: e00049
  year: 2012
  ident: ref_9
  article-title: Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus
  publication-title: eLife
  doi: 10.7554/eLife.00049
– volume: 579
  start-page: 5822
  year: 2005
  ident: ref_69
  article-title: Dicing and slicing: The core machinery of the rna interference pathway
  publication-title: FEBS Lett.
  doi: 10.1016/j.febslet.2005.08.079
– volume: 3
  start-page: e186
  year: 2014
  ident: ref_129
  article-title: The CRISPR-cas9 system facilitates clearance of the intrahepatic HBV templates in vivo
  publication-title: Mol. Ther. Nucleic Acids
  doi: 10.1038/mtna.2014.38
– volume: 18
  start-page: 378
  year: 2013
  ident: ref_22
  article-title: Creation of a six-fingered artificial transcription factor that represses the hepatitis B virus HBx gene integrated into a human hepatocellular carcinoma cell line
  publication-title: J. Biomol. Screen.
  doi: 10.1177/1087057112463066
– ident: ref_81
– volume: 267
  start-page: 12436
  year: 1992
  ident: ref_32
  article-title: Specific inhibition of hepatitis B viral gene expression in vitro by targeted antisense oligonucleotides
  publication-title: J. Biol. Chem.
  doi: 10.1016/S0021-9258(18)42295-8
– volume: 33
  start-page: 538
  year: 2015
  ident: ref_100
  article-title: Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.3190
– volume: 7
  start-page: 61
  year: 2010
  ident: ref_48
  article-title: Efficient inhibition of hepatitis B virus replication by hepatitis delta virus ribozymes delivered by targeting retrovirus
  publication-title: Virol. J.
  doi: 10.1186/1743-422X-7-61
– volume: 382
  start-page: 655
  year: 2001
  ident: ref_58
  article-title: Inhibition of hepatitis B virus by hammerhead ribozyme targeted to the poly(a) signal sequence in cultured cells
  publication-title: Biol. Chem.
  doi: 10.1515/BC.2001.077
– volume: 23
  start-page: 686
  year: 2005
  ident: ref_113
  article-title: “Magic” scissors for genome surgery
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt0605-686
– volume: 26
  start-page: 8623
  year: 2006
  ident: ref_121
  article-title: The KAP1 corepressor functions to coordinate the assembly of de novo HP1-demarcated microenvironments of heterochromatin required for KRAB zinc finger protein-mediated transcriptional repression
  publication-title: Mol. Cell. Biol.
  doi: 10.1128/MCB.00487-06
– volume: 46
  start-page: 1759
  year: 2007
  ident: ref_8
  article-title: Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans
  publication-title: Hepatology
  doi: 10.1002/hep.21896
– volume: 21
  start-page: 1889
  year: 2013
  ident: ref_26
  article-title: Inactivation of hepatitis B virus replication in cultured cells and in vivo with engineered transcription activator-like effector nucleases
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2013.170
– volume: 89
  start-page: 527
  year: 2010
  ident: ref_72
  article-title: Application of RNA interference in treating human diseases
  publication-title: J. Genet.
  doi: 10.1007/s12041-010-0073-3
– volume: 18
  start-page: 83
  year: 2014
  ident: ref_125
  article-title: Gene regulation by engineered CRISPR-Cas systems
  publication-title: Curr. Opin. Microbiol.
  doi: 10.1016/j.mib.2014.02.007
– volume: 11
  start-page: 636
  year: 2010
  ident: ref_97
  article-title: Genome editing with engineered zinc finger nucleases
  publication-title: Nat. Rev. Genet.
  doi: 10.1038/nrg2842
– volume: 30
  start-page: 457
  year: 2001
  ident: ref_21
  article-title: Ribozyme structures and mechanisms
  publication-title: Annu. Rev. Biophys. Biomol. Struct.
  doi: 10.1146/annurev.biophys.30.1.457
– volume: 23
  start-page: 1297
  year: 1996
  ident: ref_38
  article-title: Inhibition of hepatitis B virus replication by targeted pretreatment of complexed antisense DNA in vitro
  publication-title: Hepatology
  doi: 10.1002/hep.510230601
– volume: 53
  start-page: 1636
  year: 2010
  ident: ref_41
  article-title: Antisense oligonucleotides containing conformationally constrained 2′,4′-(N-methoxy)aminomethylene and 2′,4′-aminooxymethylene and 2′-O,4′-C-aminomethylene bridged nucleoside analogues show improved potency in animal models
  publication-title: J. Med. Chem.
  doi: 10.1021/jm9013295
– volume: 56
  start-page: 389
  year: 2015
  ident: ref_106
  article-title: Genome editing with engineered nucleases in plants
  publication-title: Plant Cell Physiol.
  doi: 10.1093/pcp/pcu170
– volume: 54
  start-page: 1268
  year: 2015
  ident: ref_76
  article-title: Structure-based design of novel chemical modification of the 3′-overhang for optimization of short interfering RNA performance
  publication-title: Biochemistry
  doi: 10.1021/bi500602z
– volume: 6
  start-page: 377
  year: 2000
  ident: ref_62
  article-title: Construction of HBV-specific ribozyme and its recombinant with HDV and their cleavage activity in vitro
  publication-title: World J. Gastroenterol.
  doi: 10.3748/wjg.v6.i3.377
– volume: 21
  start-page: 973
  year: 2013
  ident: ref_79
  article-title: Hepatocyte-targeted RNAi therapeutics for the treatment of chronic hepatitis B virus infection
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2013.31
– volume: 157
  start-page: 1262
  year: 2014
  ident: ref_122
  article-title: Development and applications of CRISPR-Cas9 for genome engineering
  publication-title: Cell
  doi: 10.1016/j.cell.2014.05.010
– volume: 87
  start-page: 7176
  year: 2013
  ident: ref_15
  article-title: Sodium taurocholate cotransporting polypeptide mediates woolly monkey hepatitis B virus infection of tupaia hepatocytes
  publication-title: J. Virol.
  doi: 10.1128/JVI.03533-12
– volume: 15
  start-page: 2892
  year: 2014
  ident: ref_16
  article-title: NTCP and beyond: Opening the door to unveil hepatitis B virus entry
  publication-title: Int. J. Mol. Sci.
  doi: 10.3390/ijms15022892
– volume: 41
  start-page: 1111
  year: 2006
  ident: ref_45
  article-title: Transfection and anti-HBV effect mediated by the hepatocytes-targeting cationic liposomes co-modified with β-sitosterol-β-d-glucoside and Brij 35
  publication-title: Yao Xue Xue Bao
– ident: ref_84
– volume: 21
  start-page: 383
  year: 2011
  ident: ref_4
  article-title: Countering hepatitis B virus infection using RNAi: How far are we from the clinic?
  publication-title: Rev. Med. Virol.
  doi: 10.1002/rmv.705
– volume: 30
  start-page: 828
  year: 2013
  ident: ref_42
  article-title: Antiviral effects of dual-target antisense LNA by cationic liposomes in transgenic mice
  publication-title: Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
– volume: 16
  start-page: 739
  year: 2014
  ident: ref_107
  article-title: Gene replacement by zinc finger nucleases in medaka embryos
  publication-title: Mar. Biotechnol.
  doi: 10.1007/s10126-014-9587-7
– volume: 51
  start-page: 761
  year: 2003
  ident: ref_5
  article-title: Hepatitis B virus: Old, new and future approaches to antiviral treatment
  publication-title: J. Antimicrob. Chemother.
  doi: 10.1093/jac/dkg163
– volume: 22
  start-page: 539
  year: 2012
  ident: ref_111
  article-title: Targeted chromosomal duplications and inversions in the human genome using zinc finger nucleases
  publication-title: Genome Res.
  doi: 10.1101/gr.129635.111
– volume: 42
  start-page: 463
  year: 2001
  ident: ref_47
  article-title: Targeted polynucleotides for inhibition of hepatitis B and C viruses
  publication-title: Croat. Med. J.
– volume: 8
  start-page: 91
  year: 2002
  ident: ref_53
  article-title: Anti-HBV hairpin ribozyme-mediated cleavage of target RNA in vitro
  publication-title: World J. Gastroenterol.
  doi: 10.3748/wjg.v8.i1.91
– volume: 41
  start-page: 9779
  year: 2013
  ident: ref_118
  article-title: Directed evolution of the TALE N-terminal domain for recognition of all 5′ bases
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkt754
– volume: 71 Pt 12
  start-page: 3021
  year: 1990
  ident: ref_31
  article-title: Antisense oligodeoxyribonucleotides inhibit the expression of the gene for hepatitis B virus surface antigen
  publication-title: J. Gen. Virol.
  doi: 10.1099/0022-1317-71-12-3021
– volume: 37
  start-page: 299
  year: 2015
  ident: ref_104
  article-title: A suicidal zinc finger nuclease expression coupled with a surrogate reporter for efficient genome engineering
  publication-title: Biotechnol. Lett.
  doi: 10.1007/s10529-014-1690-3
– volume: 110
  start-page: 1811
  year: 2013
  ident: ref_116
  article-title: Transcription activator-like effector nucleases (TALENs): A highly efficient and versatile tool for genome editing
  publication-title: Biotechnol. Bioeng.
  doi: 10.1002/bit.24890
– volume: 12
  start-page: 346
  year: 2005
  ident: ref_56
  article-title: Inhibition of hepatitis B virus by lentiviral vector delivered antisense RNA and hammerhead ribozymes
  publication-title: J. Viral Hepat.
  doi: 10.1111/j.1365-2893.2005.00612.x
– volume: 14
  start-page: 49
  year: 2013
  ident: ref_117
  article-title: TALENs: A widely applicable technology for targeted genome editing
  publication-title: Nat. Rev. Mol. Cell Biol.
  doi: 10.1038/nrm3486
– volume: 446
  start-page: 261
  year: 2014
  ident: ref_25
  article-title: TALE nickase mediates high efficient targeted transgene integration at the human multi-copy ribosomal DNA locus
  publication-title: Biochem. Biophys. Res. Commun.
  doi: 10.1016/j.bbrc.2014.02.099
– volume: 114
  start-page: 126
  year: 2005
  ident: ref_61
  article-title: Efficient inhibition of hepatitis B virus replication by hammerhead ribozymes delivered by hepatitis delta virus
  publication-title: Virus Res.
  doi: 10.1016/j.virusres.2005.06.005
– volume: 120
  start-page: 3106
  year: 2010
  ident: ref_88
  article-title: Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence in the adult mouse liver
  publication-title: J. Clin. Investig.
  doi: 10.1172/JCI43565
– volume: 205
  start-page: 120
  year: 2015
  ident: ref_119
  article-title: Current and future delivery systems for engineered nucleases: ZFN, TALEN and RGEN
  publication-title: J. Control. Release
  doi: 10.1016/j.jconrel.2014.12.036
– volume: 32
  start-page: 347
  year: 2014
  ident: ref_123
  article-title: CRISPR-Cas systems for editing, regulating and targeting genomes
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.2842
– volume: 15
  start-page: 321
  year: 2014
  ident: ref_96
  article-title: A guide to genome engineering with programmable nucleases
  publication-title: Nat. Rev. Genet.
  doi: 10.1038/nrg3686
– volume: 38
  start-page: 217
  year: 2007
  ident: ref_134
  article-title: Combinatorial effects of ST6Gal I siRNA and antisense oligonucleotide-mediated gene silence on metastasis ability of cervical carcinoma cells
  publication-title: Sichuan Da Xue Xue Bao Yi Xue Ban
– volume: 21
  start-page: 1406
  year: 2013
  ident: ref_10
  article-title: Assembly-directed antivirals differentially bind quasiequivalent pockets to modify hepatitis B virus capsid tertiary and quaternary structure
  publication-title: Structure
  doi: 10.1016/j.str.2013.06.013
– volume: 16
  start-page: 1105
  year: 2008
  ident: ref_91
  article-title: Expressed anti-HBV primary microRNA shuttles inhibit viral replication efficiently in vitro and in vivo
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2008.82
– volume: 3
  start-page: 19
  year: 1996
  ident: ref_34
  article-title: In vivo inhibition of hepatitis B viral gene expression by antisense phosphorothioate oligodeoxynucleotides in athymic nude mice
  publication-title: J. Viral Hepat.
  doi: 10.1111/j.1365-2893.1996.tb00076.x
– volume: 33
  start-page: 114
  year: 2005
  ident: ref_19
  article-title: Translation of stable hepadnaviral mRNA cleavage fragments induced by the action of phosphorothioate-modified antisense oligodeoxynucleotides
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gki155
– volume: 347
  start-page: 1069
  year: 2015
  ident: ref_73
  article-title: RNA interference. Drugging RNAi
  publication-title: Science
  doi: 10.1126/science.1252967
– volume: 18
  start-page: 947
  year: 2010
  ident: ref_24
  article-title: Zinc-finger nucleases as a novel therapeutic strategy for targeting hepatitis B virus DNAs
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2010.20
– volume: 231
  start-page: 397
  year: 1997
  ident: ref_64
  article-title: A minimised hammerhead ribozyme with activity against interleukin-2 in human cells
  publication-title: Biochem. Biophys. Res. Commun.
  doi: 10.1006/bbrc.1997.6099
– volume: 26
  start-page: 144
  year: 2011
  ident: ref_126
  article-title: Hepatitis B virus X protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma
  publication-title: J. Gastroenterol. Hepatol.
  doi: 10.1111/j.1440-1746.2010.06546.x
– volume: 21
  start-page: 77
  year: 2011
  ident: ref_17
  article-title: Antisense oligonucleotides targeting abhydrolase domain containing 2 block human hepatitis B virus propagation
  publication-title: Oligonucleotides
  doi: 10.1089/oli.2011.0280
– volume: 22
  start-page: 218
  year: 2014
  ident: ref_124
  article-title: To acquire or resist: The complex biological effects of CRISPR-Cas systems
  publication-title: Trends Microbiol.
  doi: 10.1016/j.tim.2014.01.007
– volume: 118
  start-page: 110
  year: 2015
  ident: ref_131
  article-title: Targeting hepatitis B virus cccDNA by CRISPR-cas9 nuclease efficiently inhibits viral replication
  publication-title: Antivir. Res.
  doi: 10.1016/j.antiviral.2015.03.015
– volume: 28
  start-page: 225
  year: 1995
  ident: ref_37
  article-title: Antisense oligonucleotides are effective inhibitors of hepatitis B virus replication in vitro
  publication-title: Antivir. Res.
  doi: 10.1016/0166-3542(95)00050-V
– ident: ref_82
– volume: 7
  start-page: 189
  year: 1999
  ident: ref_39
  article-title: Fomivirsen—A phosphorothioate oligonucleotide for the treatment of CMV retinitis
  publication-title: Ocul. Immunol. Inflamm.
  doi: 10.1076/ocii.7.3.189.4007
– volume: 82
  start-page: 8013
  year: 2008
  ident: ref_109
  article-title: Zinc finger proteins designed to specifically target duck hepatitis B virus covalently closed circular DNA inhibit viral transcription in tissue culture
  publication-title: J. Virol.
  doi: 10.1128/JVI.00366-08
– volume: 1218
  start-page: 163
  year: 2015
  ident: ref_80
  article-title: Targeted in vivo delivery of siRNA and an endosome-releasing agent to hepatocytes
  publication-title: Methods Mol. Biol.
  doi: 10.1007/978-1-4939-1538-5_10
– volume: 9
  start-page: 596
  year: 2004
  ident: ref_60
  article-title: A self-processing ribozyme cassette: Utility against human papillomavirus 11 E6/E7 mRNA and hepatitis B virus
  publication-title: Mol. Ther.
  doi: 10.1016/j.ymthe.2003.12.013
– volume: 22
  start-page: 1316
  year: 2012
  ident: ref_112
  article-title: Targeted gene addition to a predetermined site in the human genome using a ZFN-based nicking enzyme
  publication-title: Genome Res.
  doi: 10.1101/gr.122879.111
– volume: 12
  start-page: 257
  year: 2002
  ident: ref_63
  article-title: Intracellular inhibition of hepatitis B virus S gene expression by chimeric DNA-RNA phosphorothioate minimized ribozyme
  publication-title: Antisense Nucleic Acid Drug Dev.
  doi: 10.1089/108729002320351575
– volume: 22
  start-page: 338
  year: 1997
  ident: ref_67
  article-title: Design and preparation of a multimeric self-cleaving hammerhead ribozyme
  publication-title: BioTechniques
  doi: 10.2144/97222rr03
– volume: 88
  start-page: 8045
  year: 2014
  ident: ref_132
  article-title: Recombinant covalently closed circular hepatitis B virus DNA induces prolonged viral persistence in immunocompetent mice
  publication-title: J. Virol.
  doi: 10.1128/JVI.01024-14
– ident: ref_85
– volume: 9
  start-page: 411
  year: 2002
  ident: ref_57
  article-title: Characterization of nuclease-resistant ribozymes directed against hepatitis B virus RNA
  publication-title: J. Viral Hepat.
  doi: 10.1046/j.1365-2893.2002.00383.x
– volume: 40
  start-page: 35
  year: 1996
  ident: ref_35
  article-title: Inhibition of hepatitis B virus in vitro by antisense oligonucleotides
  publication-title: Acta Virol.
– volume: 24
  start-page: 739
  year: 2013
  ident: ref_87
  article-title: Studies of efficacy and liver toxicity related to adeno-associated virus-mediated RNA interference
  publication-title: Hum. Gene Ther.
  doi: 10.1089/hum.2012.239
– volume: 8
  start-page: 874
  year: 2001
  ident: ref_46
  article-title: Inhibition of hepadnaviral replication by polyethylenimine-based intravenous delivery of antisense phosphodiester oligodeoxynucleotides to the liver
  publication-title: Gene Ther.
  doi: 10.1038/sj.gt.3301464
– volume: 22
  start-page: 163
  year: 2015
  ident: ref_92
  article-title: Sustained inhibition of hepatitis B virus replication in vivo using RNAi-activating lentiviruses
  publication-title: Gene Ther.
  doi: 10.1038/gt.2014.94
– volume: 3
  start-page: e216
  year: 2014
  ident: ref_130
  article-title: Targeting hepatitis B virus with CRISPR-cas9
  publication-title: Mol. Ther. Nucleic Acids
  doi: 10.1038/mtna.2014.68
– volume: 79
  start-page: 213
  year: 2010
  ident: ref_102
  article-title: The discovery of zinc fingers and their applications in gene regulation and genome manipulation
  publication-title: Annu. Rev. Biochem.
  doi: 10.1146/annurev-biochem-010909-095056
– volume: 476
  start-page: 196
  year: 2015
  ident: ref_28
  article-title: Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR-cas RNA-guided DNA endonuclease
  publication-title: Virology
  doi: 10.1016/j.virol.2014.12.001
– ident: ref_133
– volume: 87
  start-page: 7977
  year: 2013
  ident: ref_14
  article-title: Molecular determinants of hepatitis B and D virus entry restriction in mouse sodium taurocholate cotransporting polypeptide
  publication-title: J. Virol.
  doi: 10.1128/JVI.03540-12
– volume: 21
  start-page: 995
  year: 2013
  ident: ref_52
  article-title: Inhibition of hepatitis B virus gene expression and replication by ribonuclease P
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2013.37
– volume: 136
  start-page: 215
  year: 2009
  ident: ref_68
  article-title: MicroRNAs: Target recognition and regulatory functions
  publication-title: Cell
  doi: 10.1016/j.cell.2009.01.002
– volume: 435
  start-page: 646
  year: 2005
  ident: ref_114
  article-title: Highly efficient endogenous human gene correction using designed zinc-finger nucleases
  publication-title: Nature
  doi: 10.1038/nature03556
– volume: 69
  start-page: 649
  year: 2014
  ident: ref_23
  article-title: Inhibition of hepatitis B virus cccDNA by siRNA in transgenic mice
  publication-title: Cell Biochem. Biophys.
  doi: 10.1007/s12013-014-9847-1
– volume: 22
  start-page: 404
  year: 2015
  ident: ref_29
  article-title: Harnessing the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated Cas9 system to disrupt the hepatitis B virus
  publication-title: Gene Ther.
  doi: 10.1038/gt.2015.2
– volume: 16
  start-page: 1125
  year: 2001
  ident: ref_59
  article-title: Intracellular inhibition of the replication of hepatitis B virus by hammerhead ribozymes
  publication-title: J. Gastroenterol. Hepatol.
  doi: 10.1046/j.1440-1746.2001.02548.x
– volume: 23
  start-page: 578
  year: 2008
  ident: ref_70
  article-title: Origins and evolution of eukaryotic RNA interference
  publication-title: Trends Ecol. Evol.
  doi: 10.1016/j.tree.2008.06.005
– volume: 391
  start-page: 806
  year: 1998
  ident: ref_71
  article-title: Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
  publication-title: Nature
  doi: 10.1038/35888
– volume: 16
  start-page: 1630
  year: 2008
  ident: ref_94
  article-title: Expression of shRNA from a tissue-specific Pol II promoter is an effective and safe RNAi therapeutic
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2008.144
– reference: 17461767 - Oligonucleotides. 2007 Spring;17(1):104-12
– reference: 16724069 - Nature. 2006 May 25;441(7092):537-41
– reference: 18046710 - Hepatology. 2007 Dec;46(6):1759-68
– reference: 8886096 - Acta Virol. 1996 Feb;40(1):35-9
– reference: 11405228 - Biol Chem. 2001 Apr;382(4):655-60
– reference: 10611727 - Ocul Immunol Inflamm. 1999 Dec;7(3-4):189-98
– reference: 23596296 - J Virol. 2013 Jun;87(12):7176-84
– reference: 25097139 - Mar Biotechnol (NY). 2014 Dec;16(6):739-47
– reference: 25843425 - Antiviral Res. 2015 Jun;118:110-7
– reference: 1631050 - Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5710-4
– reference: 24569930 - Cell Biochem Biophys. 2014 Jul;69(3):649-54
– reference: 16054262 - Virus Res. 2005 Dec;114(1-2):126-32
– reference: 20108935 - J Med Chem. 2010 Feb 25;53(4):1636-50
– reference: 20717154 - Nat Rev Genet. 2010 Sep;11(9):636-46
– reference: 21784508 - Lancet. 2011 Aug 13;378(9791):595-605
– reference: 24906146 - Cell. 2014 Jun 5;157(6):1262-78
– reference: 25625233 - J Hepatol. 2015 Jun;62(6):1265-71
– reference: 24059065 - Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2013 Aug;30(4):828-32, 837
– reference: 21913277 - Rev Med Virol. 2011 Nov;21(6):383-96
– reference: 18431360 - Mol Ther. 2008 Jun;16(6):1105-12
– reference: 16426595 - Clin Chim Acta. 2006 May;367(1-2):20-7
– reference: 25635512 - Biochemistry. 2015 Feb 10;54(5):1268-77
– reference: 23678176 - J Virol. 2013 Jul;87(14):7977-91
– reference: 15640448 - Nucleic Acids Res. 2005;33(1):114-25
– reference: 18524822 - J Virol. 2008 Aug;82(16):8013-21
– reference: 11471200 - Croat Med J. 2001 Aug;42(4):463-6
– reference: 25280729 - Biotechnol Lett. 2015 Feb;37(2):299-305
– reference: 1618751 - J Biol Chem. 1992 Jun 25;267(18):12436-9
– reference: 25487859 - Chembiochem. 2015 Jan 19;16(2):262-7
– reference: 20160705 - Mol Ther. 2010 May;18(5):947-54
– reference: 12238814 - Antisense Nucleic Acid Drug Dev. 2002 Aug;12(4):257-64
– reference: 23883864 - Mol Ther. 2013 Oct;21(10):1889-97
– reference: 21466387 - Oligonucleotides. 2011 Mar-Apr;21(2):77-84
– reference: 19167326 - Cell. 2009 Jan 23;136(2):215-33
– reference: 25652100 - Gene Ther. 2015 May;22(5):404-12
– reference: 24690881 - Nat Rev Genet. 2014 May;15(5):321-34
– reference: 24589733 - Biochem Biophys Res Commun. 2014 Mar 28;446(1):261-6
– reference: 23980031 - Nucleic Acids Res. 2013 Nov;41(21):9779-85
– reference: 24557582 - Int J Mol Sci. 2014;15(2):2892-905
– reference: 16039907 - Mol Ther. 2005 Oct;12(4):610-7
– reference: 23829557 - Hum Gene Ther. 2013 Aug;24(8):739-50
– reference: 25319651 - Methods Mol Biol. 2015;1218:163-86
– reference: 24932966 - Viruses. 2014 Jun;6(6):2376-91
– reference: 17262957 - Yao Xue Xue Bao. 2006 Nov;41(11):1111-5
– reference: 20038330 - Zhonghua Gan Zang Bing Za Zhi. 2009 Dec;17(12):900-4
– reference: 19952142 - Genome Res. 2010 Jan;20(1):81-9
– reference: 25137139 - Mol Ther Nucleic Acids. 2014 Aug 19;3:e186
– reference: 15093190 - Mol Ther. 2004 Apr;9(4):596-606
– reference: 18398004 - Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5868-73
– reference: 17709147 - Antiviral Res. 2007 Nov;76(2):168-77
– reference: 23871485 - Structure. 2013 Aug 6;21(8):1406-16
– reference: 8736236 - J Viral Hepat. 1996 Jan;3(1):19-22
– reference: 23481322 - Mol Ther. 2013 May;21(5):995-1003
– reference: 24582529 - Trends Microbiol. 2014 Apr;22(4):218-25
– reference: 25808449 - Retrovirology. 2015;12:22
– reference: 23508559 - Biotechnol Bioeng. 2013 Jul;110(7):1811-21
– reference: 25553825 - J Control Release. 2015 May 10;205:120-7
– reference: 25654603 - Nat Med. 2015 Feb;21(2):121-31
– reference: 25127104 - Bioorg Med Chem Lett. 2014 Sep 1;24(17):4247-9
– reference: 20221260 - PLoS Genet. 2010 Mar;6(3):e1000869
– reference: 21842305 - Pharm Res. 2012 Feb;29(2):362-74
– reference: 9070287 - Biochem Biophys Res Commun. 1997 Feb 13;231(2):397-402
– reference: 22489259 - World J Hepatol. 2012 Mar 27;4(3):74-80
– reference: 25035419 - Hum Mol Genet. 2014 Dec 1;23(23):6302-17
– reference: 25003129 - Biomed Res Int. 2014;2014:718743
– reference: 12183271 - Antimicrob Agents Chemother. 2002 Sep;46(9):3057-60
– reference: 21199526 - J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:144-52
– reference: 19474340 - Nucleic Acids Res. 2009 Jul;37(13):e91
– reference: 24382818 - Int J Cancer. 2014 Aug 1;135(3):742-50
– reference: 25167956 - J Gastroenterol Hepatol. 2015 Feb;30(2):372-8
– reference: 24807718 - J Virol. 2014 Jul;88(14):8045-56
– reference: 23169466 - Nat Rev Mol Cell Biol. 2013 Jan;14(1):49-55
– reference: 21273705 - J Genet. 2010 Dec;89(4):527-37
– reference: 23042077 - J Biomol Screen. 2013 Apr;18(4):378-87
– reference: 23150796 - Elife. 2012;1:e00049
– reference: 16214139 - FEBS Lett. 2005 Oct 31;579(26):5822-9
– reference: 24584096 - Nat Biotechnol. 2014 Apr;32(4):347-55
– reference: 9486653 - Nature. 1998 Feb 19;391(6669):806-11
– reference: 12654750 - J Antimicrob Chemother. 2003 Apr;51(4):761-85
– reference: 25416289 - Plant Cell Physiol. 2015 Mar;56(3):389-400
– reference: 11819602 - World J Gastroenterol. 2000 Jun;6(3):377-380
– reference: 25338920 - Gene Ther. 2015 Feb;22(2):163-71
– reference: 25514649 - Mol Ther Nucleic Acids. 2014 Dec 16;3:e216
– reference: 25803306 - Nat Biotechnol. 2015 May;33(5):543-8
– reference: 22434427 - Genome Res. 2012 Jul;22(7):1316-26
– reference: 18665161 - Mol Ther. 2008 Sep;16(9):1630-6
– reference: 23913666 - Genesis. 2013 Sep;51(9):605-18
– reference: 17441333 - Sichuan Da Xue Xue Bao Yi Xue Ban. 2007 Mar;38(2):217-21
– reference: 15940239 - Nat Biotechnol. 2005 Jun;23(6):686-7
– reference: 25798939 - Nat Biotechnol. 2015 May;33(5):538-42
– reference: 18715673 - Trends Ecol Evol. 2008 Oct;23(10):578-87
– reference: 8458338 - EMBO J. 1993 Mar;12(3):1257-62
– reference: 2177093 - J Gen Virol. 1990 Dec;71 ( Pt 12):3021-5
– reference: 23799901 - Hepatol Res. 2014 Aug;44(8):897-906
– reference: 11686839 - J Gastroenterol Hepatol. 2001 Oct;16(10):1125-30
– reference: 11423935 - Gene Ther. 2001 Jun;8(11):874-81
– reference: 24099962 - Eur J Pharmacol. 2013 Dec 5;721(1-3):86-95
– reference: 25553515 - Virology. 2015 Feb;476:196-205
– reference: 23439496 - Mol Ther. 2013 May;21(5):973-85
– reference: 12236779 - Bioconjug Chem. 2002 Sep-Oct;13(5):975-84
– reference: 19404258 - Nature. 2009 May 21;459(7245):442-5
– reference: 15806097 - Nature. 2005 Jun 2;435(7042):646-51
– reference: 9282175 - Gene Ther. 1997 Jul;4(7):736-43
– reference: 22183967 - Genome Res. 2012 Mar;22(3):539-48
– reference: 23664777 - Trends Biotechnol. 2013 Jul;31(7):397-405
– reference: 10679273 - Biochem Biophys Res Commun. 2000 Feb 24;268(3):728-33
– reference: 20697157 - J Clin Invest. 2010 Sep;120(9):3106-19
– reference: 15985004 - J Viral Hepat. 2005 Jul;12(4):346-56
– reference: 25271723 - J Clin Invest. 2014 Oct;124(10):4154-61
– reference: 12431202 - J Viral Hepat. 2002 Nov;9(6):411-8
– reference: 24637219 - Curr Opin Microbiol. 2014 Apr;18:83-9
– reference: 8675142 - Hepatology. 1996 Jun;23(6):1297-303
– reference: 24025750 - Mol Ther. 2014 Feb;22(2):303-11
– reference: 15698393 - Liver Int. 2005 Feb;25(1):9-15
– reference: 25729471 - World J Hepatol. 2015 Feb 27;7(2):150-64
– reference: 11441810 - Annu Rev Biophys Biomol Struct. 2001;30:457-75
– reference: 21755468 - Adv Exp Med Biol. 2011;700:1-14
– reference: 11833079 - World J Gastroenterol. 2002 Feb;8(1):91-4
– reference: 15267221 - Curr Mol Med. 2004 Aug;4(5):489-506
– reference: 19933107 - Science. 2009 Dec 11;326(5959):1509-12
– reference: 10715200 - J Mol Biol. 2000 Mar 24;297(2):269-91
– reference: 8629815 - Antiviral Res. 1995 Nov;28(3):225-42
– reference: 24827459 - PLoS One. 2014;9(5):e97579
– reference: 16954381 - Mol Cell Biol. 2006 Nov;26(22):8623-38
– reference: 20192761 - Annu Rev Biochem. 2010;79:213-31
– reference: 25745148 - Science. 2015 Mar 6;347(6226):1069-70
– reference: 20236514 - Virol J. 2010;7:61
– reference: 9043708 - Biotechniques. 1997 Feb;22(2):338-45
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Snippet Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern....
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StartPage 17589
SubjectTerms DNA, Viral - antagonists & inhibitors
DNA, Viral - genetics
Gene therapy
Genetic Therapy
Hepatitis
Hepatitis B virus
Hepatitis B virus - genetics
Hepatitis B virus - pathogenicity
Hepatitis B, Chronic - genetics
Hepatitis B, Chronic - therapy
Hepatitis B, Chronic - virology
Humans
Oligonucleotides, Antisense - therapeutic use
Review
Ribonucleic acid
RNA
RNA Editing - genetics
RNA Interference
RNA, Catalytic - genetics
RNA, Catalytic - therapeutic use
Vaccines
Virus Replication - genetics
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Title Progress and Prospects of Anti-HBV Gene Therapy Development
URI https://www.ncbi.nlm.nih.gov/pubmed/26263978
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Volume 16
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