Abo Bibliothek: Guest
Digitales Portal Digitale Bibliothek eBooks Zeitschriften Referenzen und Berichte Forschungssammlungen
Critical Reviews™ in Eukaryotic Gene Expression
Impact-faktor: 2.156 5-jähriger Impact-Faktor: 2.255 SJR: 0.649 SNIP: 0.599 CiteScore™: 3

ISSN Druckformat: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.2020028207
pages 45-56

CRISPR/CAS9-Mediated Antiviral Activity: A Tool to Combat Viral Infection

Usman Ali Ashfaq
Department of Bioinformatics & Biotechnology, Government College University, 38000 Faisalabad, Pakistan
Hina Khalid
Department of Bioinformatics and Biotechnology, Government College University, 38000 Faisalabad, Pakistan


Viruses hijack host cellular receptors and functions for replication, thereby posing a complication in identifying therapeutic targets. The CRISPR/Cas 9 platform has revolutionized gene-editing modalities in a wide range of cells and organisms with high potential in therapeutics. Recently, it has been put to work targeting human pathogenic viruses that interrupt receptors and functions with viral replication. This review encompasses major discoveries in CRISPR/Cas as an antiviral strategy. Additionally, challenges that demand consideration prior to its use in the clinic as part of the antiviral armamentarium are briefly addressed.


  1. Goldberg GW, Marraffini LA. Resistance and tolerance to foreign elements by prokaryotic immune systems-curating the genome. Nature Rev Immunol. 2015;15(11):717-24.

  2. Marraffini LA. CRISPR-Cas immunity in prokaryotes. Nature. 2015;526(7571):55-61.

  3. Makarova KS, Wolf YI, Koonin EV. Comparative genomics of defense systems in archaea and bacteria. Nucleic Acids Res. 2013;41(8):4360-77.

  4. Mojica FJ, Garcia-Martinez J, Soria E. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evolution. 2005;60(2):174-82.

  5. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P. CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007;315(5819):1709-12.

  6. YosefI, Goren MG, Qimron U. Proteins and DNA elements essential for the CRISPR adaptation process in Escherichia coli. Nucleic Acids Res. 2012;40(12):5569-76.

  7. Barrangou R. Diversity of CRISPR-Cas immune systems and molecular machines. Genome Biol. 2015;16(1):247.

  8. Garneau JE, Dupuis M-E, Villion M, Romero DA, Barrangou R, Boyaval P, Fremaux C, Horvath P, Magadan AH, Moineau S. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature. 2010;468(7320):67-71.

  9. Mohanraju P, Makarova KS, Zetsche B, Zhang F, Koonin EV, van der Oost J. Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems. Science. 2016;353(6299):aad5147.

  10. Marraffini LA, Sontheimer EJ. Self versus non-self discrimination during CRISPR RNA-directed immunity. Nature. 2010;463(7280):568-71.

  11. Mojica F, Diez-Villasenor C, Garcia-Martinez J, Almendros C. Short motif sequences determine the targets of the prokaryotic CRISPR defence system. Microbiology. 2009;155(3):733-40.

  12. Horvath P, Romero DA, Coute-Monvoisin A-C, Richards M, Deveau H, Moineau S, Boyaval P, Fremaux C, Barrangou R. Diversity, activity, and evolution of CRISPR loci in Streptococcus thermophilus. J Bacteriol. 2008;190(4):1401-12.

  13. Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J. RNA-programmed genome editing in human cells. eLife. 2013;2:e00471.

  14. Sternberg SH, Doudna JA. Expanding the biologist's toolkit with CRISPR-Cas9. Mol Cell. 2015;58(4):568-74.

  15. Gaj T, Gersbach CA, Barbas CF. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31(7):397-405.

  16. Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating and targeting genomes. Nature Biotechnol. 2014;32(4):347-55.

  17. Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014;157(6):1262-78.

  18. Cox DBT, Platt RJ, Zhang F. Therapeutic genome editing: prospects and challenges. Nature Med. 2015;21(2):121-31.

  19. Price AA, Grakoui A, Weiss DS. Harnessing the prokaryotic adaptive immune system as a eukaryotic antiviral defense. Trends Microbiol. 2016;24(4):294-306.

  20. White MK, Hu W, Khalili K. The CRISPR/Cas9 genome editing methodology as a weapon against human viruses. Discov Med. 2015;19(105):255.

  21. Kennedy EM, Cullen BR. Bacterial CRISPR/Cas DNA endonucleases: a revolutionary technology that could dramatically impact viral research and treatment. Virology. 2015;479:213-20.

  22. Zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nature Rev Cancer. 2002;2(5):342-50.

  23. Moody CA, Laimins LA. Human papillomavirus oncoproteins: pathways to transformation. Nature Rev Cancer. 2010;10(8):550-60.

  24. Kennedy EM, Kornepati AV, Goldstein M, Bogerd HP, Poling BC, Whisnant AW, Kastan MB, Cullen BR. Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease. J Virol. 2014; 88(20):11965-72.

  25. Hu Z, Yu L, Zhu D, Ding W, Wang X, Zhang C, Wang L, Jiang X, Shen H, He D. Disruption of HPV16-E7 by CRISPR/Cas system induces apoptosis and growth inhibition in HPV16 positive human cervical cancer cells. BioMed Res Int. 2014;2014:1-9.

  26. Zhen S, Hua L, Takahashi Y, Narita S, Liu Y-H, Li Y. In vitro and in vivo growth suppression of human papilloma-virus 16-positive cervical cancer cells by CRISPR/Cas9. Biochem Biophys Res Commun. 2014;450(4):1422-6.

  27. Liu Y-C, Cai Z-M, Zhang X-J. Reprogrammed CRIS-PR-Cas9 targeting the conserved regions of HPV6/11 E7 genes inhibits proliferation and induces apoptosis in E7-transformed keratinocytes. Asian J Androl. 2016;18(3):475.

  28. Yu L, Wang X, Zhu D, Ding W, Wang L, Zhang C, Jiang X, Shen H, Liao S, Ma D. Disruption of human papilloma-virus 16 E6 gene by clustered regularly interspaced short palindromic repeat/Cas system in human cervical cancer cells. OncoTargets Ther. 2015;8:37.

  29. Jiang M, Abend JR, Johnson SF, Imperiale MJ. The role of polyomaviruses in human disease. Virology. 2009;384(2):266-73.

  30. Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, Lee S, Plavina T, Scanlon JV, Sandrock A. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870-80.

  31. Chou Y-Y, Krupp A, Kaynor C, Gaudin R, Ma M, Cahir-McFarland E, Kirchhausen T. Inhibition of JCPyV infection mediated by targeted viral genome editing using CRISPR/Cas9. Sci Rep. 2016;6:36921.

  32. Wollebo HS, Bellizzi A, Kaminski R, Hu W, White MK, Khalili K. CRISPR/Cas9 system as an agent for eliminating polyomavirus JC infection. PLoS One. 2015;10(9):e0136046.

  33. Horst D, Ressing ME, Wiertz EJ. Exploiting human herpesvirus immune evasion for therapeutic gain: potential and pitfalls. Immunol Cell Biol. 2011;89(3):359-66.

  34. Coen DM, Schaffer PA. Antiherpesvirus drugs: a promising spectrum of new drugs and drug targets. Nature Rev Drug Discov. 2003;2(4):278-88.

  35. van Diemen FR, Kruse EM, Hooykaas MJ, Bruggeling CE, Schurch AC, van Ham PM, Imhof SM, Nijhuis M, Wiertz EJ, Lebbink RJ. CRISPR/Cas9-mediated genome editing of herpesviruses limits productive and latent infections. PLoS Pathogens. 2016;12(6):e1005701.

  36. Wang J, Quake SR. RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection. Proc Natl Acad Sci USA. 2014;111(36):13157-62.

  37. Roehm PC, Shekarabi M, Wollebo HS, Bellizzi A, He L, Salkind J, Khalili K. Inhibition of HSV-1 replication by gene editing strategy. Sci Rep. 2016;6:23146.

  38. Taylor GS, Long HM, Brooks JM, Rickinson AB, Hislop AD. The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol. 2015;33:787-821.

  39. Ok CY, Li L, Young KH. EBV-driven B-cell lymphopro-liferative disorders: from biology, classification and differential diagnosis to clinical management. Exper Mol Med. 2015;47(1):e132.

  40. Rowe M, Lear A, Croom-Carter D, Davies A, Rickinson A. Three pathways of Epstein-Barr virus gene activation from EBNA1-positive latency in B lymphocytes. J Virol. 1992;66(1):122-31.

  41. Rawlins DR, Milman G, Hayward SD, Hayward GS. Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell. 1985;42(3):859-68.

  42. Abbot S, Rowe M, Cadwallader K, Ricksten A, Gordon J, Wang F, Rymo L, Rickinson A. Epstein-Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein. J Virol. 1990;64(5):2126-34.

  43. Wakisaka N, Pagano JS. Epstein-Barr virus induces invasion and metastasis factors. Anticancer Res. 2003; 23(3A):2133-8.

  44. Yuen K-S, Chan C-P, Wong N-HM, Ho C-H, Ho T-H, Lei T, Deng W, Tsao SW, Chen H, Kok K-H. CRISPR/Cas9-mediated genome editing of Epstein-Barr virus in human cells. J General Virol. 2015;96(3):626-36.

  45. Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, Yamanishi K. Human herpesviruses: biology, therapy, and immunoprophylaxis. Cambridge, UK: University Press; 2007.

  46. Roizman B, Whitley RJ. An inquiry into the molecular basis of HSV latency and reactivation. Annu Rev Microbiol. 2013;67:355-74.

  47. Liesegang TJ. Epidemiology of ocular herpes simplex: natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989;107(8):1160-5.

  48. Horlbeck MA, Witkowsky LB, Guglielmi B, Replogle JM, Gilbert LA, Villalta JE, Torigoe SE, Tijan R, Weissman JS. Nucleosomes impede Cas9 access to DNA in vivo and in vitro. eLife. 2016;5:e12677.

  49. Griffiths PD. Burden of disease associated with human cytomegalovirus and prospects for elimination by universal immunisation. Lancet Infect Dis. 2012;12(10):790-8.

  50. Arzumanyan A, Reis HM, Feitelson MA. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer. 2013;13(2):123-35.

  51. Trepo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014;384(9959):2053-63.

  52. Lin S-R, Yang H-C, Kuo Y-T, Liu C-J, Yang T-Y, Sung K-C, Lin Y-Y, Wang H-Y, Wang C-C, Shen Y-C. The CRISPR/ Cas9 system facilitates clearance of the intrahepatic HBV templates in vivo. Mol Ther-Nucleic Acids. 2014;3:e186.

  53. Ramanan V, Shlomai A, Cox DB, Schwartz RE, Michailidis E, Bhatta A, Scott DA, Zhang F, Rice CM, Bhatia SN. CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus. Sci Rep. 2015;5:10833. doi: 10.1038/srep10833.

  54. Liu X, Hao R, Chen S, Guo D, Chen Y. Inhibition of hepatitis B virus by the CRISPR/Cas9 system via targeting the conserved regions of the viral genome. J General Virol. 2015;96(8):2252-61.

  55. Zhen S, Hua L, Liu Y, Gao L, Fu J, Wan D, Dong L, Song H, Gao X. Harnessing the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated Cas9 system to disrupt the hepatitis B virus. Gene Ther. 2015;22(5):404-12.

  56. Dong C, Qu L, Wang H, Wei L, Dong Y, Xiong S. Targeting hepatitis B virus cccDNA by CRISPR/Cas9 nuclease efficiently inhibits viral replication. Antiviral Res. 2015;118:110-7.

  57. Barre-Sinoussi F, Ross AL, Delfraissy J-F. Past, present and future: 30 years of HIV research. Nat Rev Microbiol. 2013;11(12):877-83.

  58. Okoye AA, Picker LJ. CD4+ T-cell depletion in HIV infection: mechanisms of immunological failure. Immunol Rev. 2013;254(1):54-64.

  59. McElrath MJ, Haynes BF. Induction of immunity to human immunodeficiency virus type-1 by vaccination. Immunity. 2010;33(4):542-54.

  60. Haynes BF. New approaches to HIV vaccine development. Curr Op Immunol. 2015;35:39-47.

  61. Martin AR, Siliciano RF. Progress toward HIV eradication: case reports, current efforts, and the challenges associated with cure. Annu Rev Med. 2016;67:215-28.

  62. Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H, Koup RA, Landau NR. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996;86(3):367-77.

  63. Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K, Schneider T, Hofmann J, Kucherer C, Blau O. Long-term control ofHIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med. 2009;360(7):692-8.

  64. Allers K, Hutter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T. Evidence for the cure of HIV infection by CCR5A32/A32 stem cell transplantation. Blood. 2011;117(10):2791-9.

  65. Ye L, Wang J, Beyer AI, Teque F, Cradick TJ, Qi Z, Chang JC, Bao G, Muench MO, Yu J. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5A32 mutation confers resistance to HIV infection. Proc Natl Acad Sci USA. 2014;111(26):9591-6.

  66. Connor RI, Sheridan KE, Ceradini D, Choe S, Landau NR. Change in coreceptor use correlates with disease progression in HIV-1-infected individuals. J Exper Med. 1997;185(4):621-8.

  67. Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, Nagler A, Ben-Hur H, Many A, Shultz L. Dependence of human stem cell engraftment and repopulation of NOD/ SCID mice on CXCR4. Science. 1999;283(5403):845-8.

  68. Yuan J, Wang J, Crain K, Fearns C, Kim KA, Hua KL, Gregory PD, Holmes MC, Torbett BE. Zinc-finger nuclease editing of human CXCR4 promotes HIV-1 CD4+ T cell resistance and enrichment. Mol Ther. 2012;20(4): 849-59.

  69. Wilen CB, Wang J, Tilton JC, Miller JC, Kim KA, Rebar EJ, Sherrill-Mix SA, Patro SC, Secreto AJ, Jordan AP. Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases. PLoS Pathogens. 2011;7(4):e1002020.

  70. Hou P, Chen S, Wang S, Yu X, Chen Y, Jiang M, Zhuang K, Ho W, Hou W, Huang J. Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection. Sci Rep. 2015;5:15577.

  71. Ebina H, Misawa N, Kanemura Y, Koyanagi Y. Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus. Sci Rep. 2013;3:2510. doi: 10.1038/srep02510.

  72. Hu W, Kaminski R, Yang F, Zhang Y, Cosentino L, Li F, Luo B, Alvarez-Carbonell D, Garcia-Mesa Y, Karn J. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. Proc Natl Acad Sci USA. 2014;111(31):11461-6.

  73. Liao H-K, Gu Y, Diaz A, Marlett J, Takahashi Y, Li M, Suzuki K, Xu R, Hishida T, Chang C-J. Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells. Nat Commun. 2015;6:6413.

  74. Kaminski R, Chen Y, Salkind J, Bella R, Young W-B, Ferrante P, Karn J, Malcolm T, Hu W, Khalili K. Negative feedback regulation of HIV-1 by gene editing strategy. Sci Rep. 2016;6:31527.

  75. Zhu W, Lei R, Le Duff Y, Li J, Guo F, Wainberg MA, Liang C. The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA. Retrovirology. 2015;12(1):22.

  76. Yin C, Zhang T, Li F, Yang F, Putatunda R, Young W-B, Khalili K, Hu W, Zhang Y. Functional screening of guide RNAs targeting the regulatory and structural HIV-1 viral genome for a cure of AIDS. Aids. 2016;30(8):1163-74.

  77. Kaminski R, Bella R, Yin C, Otte J, Ferrante P, Gendelman HE, Li H, Booze R, Gordon J, Hu W. Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study. Gene Ther. 2016;23(8):690-5.

  78. Yoder KE, Bundschuh R. Host double strand break repair generates HIV-1 strains resistant to CRISPR/Cas9. Sci Rep. 2016;6:29530. doi: 10.1038/srep29530.

  79. Ueda S, Ebina H, Kanemura Y, Misawa N, Koyanagi Y. Anti-HIV-1 potency of the CRISPR/Cas9 system insufficient to fully inhibit viral replication. Microbiol Immunol. 2016;60(7):483-96.

  80. Lebbink RJ, De Jong DC, Wolters F, Kruse EM, Van Ham PM, Wiertz EJ, Nijhuis M. A combinational CRISPR/Cas9 gene-editing approach can halt HIV replication and prevent viral escape. Sci Rep. 2017;7:41968. doi: 10.1038/ srep41968.

  81. Wang G, Zhao N, Berkhout B, Das AT. A combinatorial CRISPR-Cas9 attack on HIV-1 DNA extinguishes all infectious provirus in infected T cell cultures. Cell Rep. 2016;17(11):2819-26.

  82. Rasmussen TA, Lewin SR. Shocking HIV out of hiding: where are we with clinical trials of latency reversing agents? Curr Op HIV AIDS. 2016;11(4):394-401.

  83. Dominguez AA, Lim WA, Qi LS. Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation. Nat Rev Mol Cell Biol. 2016;17(1):5-15.

  84. Bialek JK, Dunay GA, Voges M, Schafer C, Spohn M, Stucka R, Hauber J, Lange UC. Targeted HIV-1 latency reversal using CRISPR/Cas9-derived transcriptional activator systems. PLoS One. 2016;11(6):e0158294.

  85. Limsirichai P, Gaj T, Schaffer DV. CRISPR-mediated activation of latent HIV-1 expression. Mol Ther. 2016;24(3):499-507.

  86. Saayman SM, Lazar DC, Scott TA, Hart JR, Takahashi M, Burnett JC, Planelles V, Morris KV, Weinberg MS. Potent and targeted activation of latent HIV-1 using the CRISPR/dCas9 activator complex. Mol Ther. 2016;24(3):488-98.

  87. Ji H, Jiang Z, Lu P, Ma L, Li C, Pan H, Fu Z, Qu X, Wang P, Deng J. Specific reactivation of latent HIV-1 by dCas9-SunTag-VP64-mediated guide RNA targeting the HIV-1 promoter. Mol Ther. 2016;24(3):508-21.

  88. Bogerd HP, Kornepati AV, Marshall JB, Kennedy EM, Cullen BR. Specific induction of endogenous viral restriction factors using CRISPR/Cas-derived transcriptional activators. Proc Natl Acad Sci USA. 2015;112(52):E7249-E56.

  89. Thrift AP, El-Serag HB, Kanwal F. Global epidemiology and burden of HCV infection and HCV-related disease. Nat Rev Gastroenterol Hepatol. 2017;14(2):122-32.

  90. Simmonds P, Bukh J, Combet C, Deleage G, Enomoto N, Feinstone S, Halfon P, Inchauspe G, Kuiken C, Maertens G. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology. 2005;42(4):962-73.

  91. Rosen HR. Chronic hepatitis C infection. N Engl J Med. 2011;364(25):2429-38.

  92. McQuaid T, Savini C, Seyedkazemi S. Sofosbuvir, a significant paradigm change in HCV treatment. J Clin Trans Hepatol. 2015;3(1):27.

  93. Lawitz E, Lalezari JP, Hassanein T, Kowdley KV, Poordad FF, Sheikh AM, Afdhal NH, Bernstein DE, DeJesus E, Freilich B. Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis. 2013;13(5):401-8.

  94. Poveda E, Wyles DL, Mena A, Pedreira JD, Castro-Iglesias A, Cachay E. Update on hepatitis C virus resistance to direct-acting antiviral agents. Antiviral Res. 2014;108:181-91.

  95. Wyles DL. Antiviral resistance and the future landscape of hepatitis C virus infection therapy. J Infect Dis. 2013;207(Suppl 1):S33-S9.

  96. Price AA, Sampson TR, Ratner HK, Grakoui A, Weiss DS. Cas9-mediated targeting of viral RNA in eukaryotic cells. Proc Natl Acad Sci USA. 2015;112(19):6164-9.

  97. Senis E, Mockenhaupt S, Rupp D, Bauer T, Paramasivam N, Knapp B, Gronych J, Grosse S, Windisch MP, Schmidt F. TALEN/CRISPR-mediated engineering of a promoterless anti-viral RNAi hairpin into an endogenous miRNA locus. Nucleic Acids Res. 2017;45(1):13-7.

  98. Wang Z, Pan Q, Gendron P, Zhu W, Guo F, Cen S, Wainberg MA, Liang C. CRISPR/Cas9-derived mutations both inhibit HIV-1 replication and accelerate viral escape. Cell Rep. 2016;15(3):481-9.

  99. Yoshinouchi M, Yamada T, Kizaki M, Fen J, Koseki T, Ikeda Y, Nishihara T, Yamato K. In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by E6 siRNA. Mol Ther. 2003;8(5):762-8.

  100. Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, Essletzbichler P, Volz SE, Joung J, van der Oost J, Regev A, Koonin EV, Zhang F. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell. 2015;163:759-771.

  101. Zhu W, Xie K, Xu Y, Wang L, Chen K, Zhang L, Fang J. CRISPR/Cas9 produces anti-hepatitis B virus effect in hepatoma cells and transgenic mouse. Virus Res. 2016;217:125-32.

  102. Kumar M, Keller B, Makalou N, Sutton RE. Systematic determination of the packaging limit of lentiviral vectors. Hum Gene Ther. 2001;12(15):1893-905.

  103. Chew WL, Tabebordbar M, Cheng JK, Mali P, Wu EY, Ng AH, Zhu K, Wagers AJ, Church GM. A multifunctional AAV-CRISPR-Cas9 and its host response. Nat Methods. 2016;13(10):868-74.

  104. Wang D, Mou H, Li S, Li Y, Hough S, Tran K, Li J, Yin H, Anderson DG, Sontheimer EJ. Adenovirus-mediated somatic genome editing of PTEN by CRISPR/Cas9 in mouse liver in spite of Cas9-specific immune responses. Hum Gene Ther. 2015;26(7):432-42.

  105. Choi J, Dang Y, Abraham S, Ma H, Zhang J, Guo H, Cai Y, Mikkelsen J, Wu H, Shankar P. Lentivirus pre-packed with Cas9 protein for safer gene editing. Gene Ther. 2016;23(7):627-33.

  106. Gu W-G. Genome editing-based HIV therapies. Trends Biotechnol. 2015;33(3):172-9.

  107. Gori JL, Hsu PD, Maeder ML, Shen S, Welstead GG, Bumcrot D. Delivery and specificity of CRISPR/Cas9 genome editing technologies for human gene therapy. Hum Gene Ther. 2015;26(7):443-51.

  108. Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol. 2013;31(9):822-6.

  109. Ran FA, Hsu PD, Lin C-Y, Gootenberg JS, Konermann S, Trevino AE, Scott DA, Inoue A, Matoba S, Zhang Y. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell. 2013;154(6): 1380-9.

  110. Nelson CE, Hakim CH, Ousterout DG, Thakore PI, Moreb EA, Rivera RMC, Madhavan S, Pan X, Ran FA, Yan WX. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science. 2016;351(6271):403-7.

  111. Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, Zheng Z, Gonzales AP, Li Z, Peterson RT, Yeh J-RJ. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature. 2015;523(7561):481-5.

  112. Kleinstiver BP, Prew MS, Tsai SQ, Nguyen NT, Topkar VV, Zheng Z, Joung JK. Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition. Nat Biotechnol. 2015;33(12):1293-8.

  113. Kleinstiver BP, Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng Z, Joung JK. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016;529(7587):490-5.

Articles with similar content:

MicroRNAs in Human Lymphoblastoid Cell Lines
Critical Reviews™ in Eukaryotic Gene Expression, Vol.22, 2012, issue 3
Jun-Woo Kim, Jae-Eun Lee, Bok-Ghee Han, Jae-Pil Jeon, Sung-Mi Shim, Hye-Young Nam
Roles of Steroid Receptor Coactivator 3 in Host Defense Against Bacterial Pathogens
Critical Reviews™ in Immunology, Vol.38, 2018, issue 3
Pingli Mo, Chundong Yu, Wenbo Chen
Human High Molecular Weight-Melanoma-Associated Antigen (HMW-MAA): A Melanoma Cell Surface Chondroitin Sulfate Proteoglycan (MSCP) with Biological and Clinical Significance
Critical Reviews™ in Immunology, Vol.24, 2004, issue 4
Soldano Ferrone, Xinhui Wang, Toshiro Kageshita, Chien-Chung Chang, Michael R. Campoli, James B. McCarthy
Reinvigorating Exhausted T Cells by Blockade of the PD-1 Pathway
Forum on Immunopathological Diseases and Therapeutics, Vol.6, 2015, issue 1-2
Haydn T Kissick, Eunseon Ahn, Junghwa Lee, Rafi Ahmed
CD5 as a Target for Immune-Based Therapies
Critical Reviews™ in Immunology, Vol.35, 2015, issue 2
Fernando Aranda, Marc Orta, Ines Simoes, Marta Consuegra-Fernandez, Francisco Lozano, Adelaida Sarukhan