Advertisement

Journal of NeuroVirology

, Volume 21, Issue 3, pp 310–321 | Cite as

Genome editing strategies: potential tools for eradicating HIV-1/AIDS

  • Kamel Khalili
  • Rafal Kaminski
  • Jennifer Gordon
  • Laura Cosentino
  • Wenhui Hu
Review

Abstract

Current therapy for controlling human immunodeficiency virus (HIV-1) infection and preventing acquired immunodeficiency syndrome (AIDS) progression has profoundly decreased viral replication in cells susceptible to HIV-1 infection, but it does not eliminate the low level of viral replication in latently infected cells, which contain integrated copies of HIV-1 proviral DNA. There is an urgent need for the development of HIV-1 genome eradication strategies that will lead to a permanent or “sterile” cure of HIV-1/AIDS. In the past few years, novel nuclease-initiated genome editing tools have been developing rapidly, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR/Cas9 system. These surgical knives, which can excise any genome, provide a great opportunity to eradicate the HIV-1 genome by targeting highly conserved regions of the HIV-1 long terminal repeats or essential viral genes. Given the time consuming and costly engineering of target-specific ZFNs and TALENs, the RNA-guided endonuclease Cas9 technology has emerged as a simpler and more versatile technology to allow permanent removal of integrated HIV-1 proviral DNA in eukaryotic cells, and hopefully animal models or human patients. The major unmet challenges of this approach at present include inefficient nuclease gene delivery, potential off-target cleavage, and cell-specific genome targeting. Nanoparticle or lentivirus-mediated delivery of next generation Cas9 technologies including nickase or RNA-guided FokI nuclease (RFN) will further improve the potential for genome editing to become a promising approach for curing HIV-1/AIDS.

Keywords

Genome editing CRISPR/Cas9 HIV-1 integration Latent reservoir Cure Animal models 

Notes

Acknowledgments

The authors thank past and present members of the Department of Neuroscience and the Center for Neurovirology. We also thank C. Papaleo for editorial assistance. This work was supported by R01NS087971 (W.H., K.K.) and P30MH092177 (K.K.).

Conflict of interests

The authors declare that they have no conflict of interests.

References

  1. Allers K, Hutter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T (2011) Evidence for the cure of HIV infection by CCR5Delta32/Delta32 stem cell transplantation. Blood 117:2791–2799CrossRefPubMedGoogle Scholar
  2. Archin NM, Bateson R, Tripathy MK, Crooks AM, Yang KH, Dahl NP, Kearney MF, Anderson EM, Coffin JM, Strain MC, Richman DD, Robertson KR, Kashuba AD, Bosch RJ, Hazuda DJ, Kuruc JD, Eron JJ, Margolis DM (2014) HIV-1 expression within resting CD4+ T cells after multiple doses of vorinostat. J Infect Dis 210:728–735CrossRefPubMedGoogle Scholar
  3. Arnould S, Delenda C, Grizot S, Desseaux C, Paques F, Silva GH, Smith J (2011) The I-CreI meganuclease and its engineered derivatives: applications from cell modification to gene therapy. Protein Eng Des Sel 24:27–31CrossRefPubMedGoogle Scholar
  4. Aubert M, Ryu BY, Banks L, Rawlings DJ, Scharenberg AM, Jerome KR (2011) Successful targeting and disruption of an integrated reporter lentivirus using the engineered homing endonuclease Y2 I-AniI. PLoS ONE 6:e16825CrossRefPubMedCentralPubMedGoogle Scholar
  5. Bae S, Park J, Kim JS (2014) Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases. Bioinformatics 30:1473–1475CrossRefPubMedCentralPubMedGoogle Scholar
  6. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P (2007) CRISPR provides acquired resistance against viruses in prokaryotes. Science 315:1709–1712CrossRefPubMedGoogle Scholar
  7. Battistini A, Sgarbanti M (2014) HIV-1 latency: an update of molecular mechanisms and therapeutic strategies. Viruses 6:1715–1758CrossRefPubMedCentralPubMedGoogle Scholar
  8. Bi Y, Sun L, Gao D, Ding C, Li Z, Li Y, Cun W, Li Q (2014) High-efficiency targeted editing of large viral genomes by RNA-guided nucleases. PLoS Pathog 10:e1004090CrossRefPubMedCentralPubMedGoogle Scholar
  9. Burke BP, Boyd MP, Impey H, Breton LR, Bartlett JS, Symonds GP, Hutter G (2014) CCR5 as a natural and modulated target for inhibition of HIV. Viruses 6:54–68CrossRefPubMedCentralGoogle Scholar
  10. Chen H, Choi J, Bailey S (2014) Cut site selection by the two nuclease domains of the Cas9 RNA-guided endonuclease. J Biol Chem 289:13284–13294CrossRefPubMedCentralPubMedGoogle Scholar
  11. Cho SW, Kim S, Kim JM, Kim JS (2013) Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol 31:230–232CrossRefPubMedGoogle Scholar
  12. Cho SW, Kim S, Kim Y, Kweon J, Kim HS, Bae S, Kim JS (2014) Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases. Genome Res 24:132–141CrossRefPubMedCentralPubMedGoogle Scholar
  13. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823CrossRefPubMedCentralPubMedGoogle Scholar
  14. Cradick TJ, Fine EJ, Antico CJ, Bao G (2013) CRISPR/Cas9 systems targeting beta-globin and CCR5 genes have substantial off-target activity. Nucleic Acids Res 41:9584–9592CrossRefPubMedCentralPubMedGoogle Scholar
  15. Didigu CA, Wilen CB, Wang J, Duong J, Secreto AJ, Danet-Desnoyers GA, Riley JL, Gregory PD, June CH, Holmes MC, Doms RW (2014) Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection. Blood 123:61–69CrossRefPubMedCentralPubMedGoogle Scholar
  16. Ebina H, Misawa N, Kanemura Y, Koyanagi Y (2013) Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus. Sci Rep 3:2510CrossRefPubMedCentralPubMedGoogle Scholar
  17. Fadel HJ, Morrison JH, Saenz DT, Fuchs JR, Kvaratskhelia M, Ekker SC, Poeschla EM (2014) TALEN knockout of the PSIP1 gene in human cells: analyses of HIV-1 replication and allosteric integrase inhibitor mechanism. J Virol 88:9704–9717CrossRefPubMedCentralPubMedGoogle Scholar
  18. Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD (2013) High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol 31:822–826CrossRefPubMedCentralPubMedGoogle Scholar
  19. Fu Y, Sander JD, Reyon D, Cascio VM, Joung JK (2014) Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol 32:279–284CrossRefPubMedCentralPubMedGoogle Scholar
  20. Gabriel R, Lombardo A, Arens A, Miller JC, Genovese P, Kaeppel C, Nowrouzi A, Bartholomae CC, Wang J, Friedman G, Holmes MC, Gregory PD, Glimm H, Schmidt M, Naldini L, von Kalle C (2011) An unbiased genome-wide analysis of zinc-finger nuclease specificity. Nat Biotechnol 29:816–823CrossRefPubMedGoogle Scholar
  21. Gasiunas G, Barrangou R, Horvath P, Siksnys V (2012) Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci U S A 109:E2579–E2586CrossRefPubMedCentralPubMedGoogle Scholar
  22. Guilinger JP, Pattanayak V, Reyon D, Tsai SQ, Sander JD, Joung JK, Liu DR (2014a) Broad specificity profiling of TALENs results in engineered nucleases with improved DNA-cleavage specificity. Nat Methods 11:429–435CrossRefPubMedCentralPubMedGoogle Scholar
  23. Guilinger JP, Thompson DB, Liu DR (2014b) Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat Biotechnol 32:577–582CrossRefPubMedCentralPubMedGoogle Scholar
  24. Hauber I, Hofmann-Sieber H, Chemnitz J, Dubrau D, Chusainow J, Stucka R, Hartjen P, Schambach A, Ziegler P, Hackmann K, Schrock E, Schumacher U, Lindner C, Grundhoff A, Baum C, Manz MG, Buchholz F, Hauber J (2013) Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. PLoS Pathog 9:e1003587CrossRefPubMedCentralPubMedGoogle Scholar
  25. Heckl D, Kowalczyk MS, Yudovich D, Belizaire R, Puram RV, McConkey ME, Thielke A, Aster JC, Regev A, Ebert BL (2014) Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing. Nat BiotechnolGoogle Scholar
  26. Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC, Zeitler B, Cherone JM, Meng X, Hinkley SJ, Rebar EJ, Gregory PD, Urnov FD, Jaenisch R (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29:731–734CrossRefPubMedCentralPubMedGoogle Scholar
  27. Holkers M, Maggio I, Liu J, Janssen JM, Miselli F, Mussolino C, Recchia A, Cathomen T, Goncalves MA (2013) Differential integrity of TALE nuclease genes following adenoviral and lentiviral vector gene transfer into human cells. Nucleic Acids Res 41:e63CrossRefPubMedCentralPubMedGoogle Scholar
  28. Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, Crooks GM, Kohn DB, Gregory PD, Holmes MC, Cannon PM (2010) Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol 28:839–847CrossRefPubMedCentralPubMedGoogle Scholar
  29. Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O, Cradick TJ, Marraffini LA, Bao G, Zhang F (2013) DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol 31:827–832CrossRefPubMedCentralPubMedGoogle Scholar
  30. Hsu PD, Lander ES, Zhang F (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell 157:1262–1278CrossRefPubMedCentralPubMedGoogle Scholar
  31. Hu W, Kaminski R, Yang F, Zhang Y, Cosentino L, Li F, Luo B, Alvarez-Carbonell D, Garcia-Mesa Y, Karn J, Mo X, Khalili K (2014) RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. Proc Natl Acad Sci U S A 111:11461–11466CrossRefPubMedCentralPubMedGoogle Scholar
  32. Izmiryan A, Basmaciogullari S, Henry A, Paques F, Danos O (2011) Efficient gene targeting mediated by a lentiviral vector-associated meganuclease. Nucleic Acids Res 39:7610–7619CrossRefPubMedCentralPubMedGoogle Scholar
  33. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821CrossRefPubMedGoogle Scholar
  34. Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J (2013) RNA-programmed genome editing in human cells. Elife 2:e00471CrossRefPubMedCentralPubMedGoogle Scholar
  35. Joung JK, Sander JD (2013) TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol 14:49–55CrossRefPubMedCentralPubMedGoogle Scholar
  36. Karvelis T, Gasiunas G, Siksnys V (2013) Programmable DNA cleavage in vitro by Cas9. Biochem Soc Trans 41:1401–1406PubMedGoogle Scholar
  37. Kennedy EM, Kornepati AV, Goldstein M, Bogerd HP, Poling BC, Whisnant AW, Kastan MB, Cullen BR (2014) Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease. J Virol 88:11965–11972CrossRefPubMedCentralPubMedGoogle Scholar
  38. Kim YG, Cha J, Chandrasegaran S (1996) Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci U S A 93:1156–1160CrossRefPubMedCentralPubMedGoogle Scholar
  39. Kim JM, Kim D, Kim S, Kim JS (2014) Genotyping with CRISPR-Cas-derived RNA-guided endonucleases. Nat Commun 5:3157PubMedGoogle Scholar
  40. Koike-Yusa H, Li Y, Tan EP, Velasco-Herrera Mdel C, Yusa K (2014) Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat Biotechnol 32:267–273CrossRefPubMedGoogle Scholar
  41. Kumar A, Abbas W, Herbein G (2014) HIV-1 latency in monocytes/macrophages. Viruses 6:1837–1860CrossRefPubMedCentralPubMedGoogle Scholar
  42. Kuscu C, Arslan S, Singh R, Thorpe J, Adli M (2014) Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease. Nat BiotechnolGoogle Scholar
  43. Lee HJ, Kim E, Kim JS (2010) Targeted chromosomal deletions in human cells using zinc finger nucleases. Genome Res 20:81–89CrossRefPubMedCentralPubMedGoogle Scholar
  44. Li L, Krymskaya L, Wang J, Henley J, Rao A, Cao LF, Tran CA, Torres-Coronado M, Gardner A, Gonzalez N, Kim K, Liu PQ, Hofer U, Lopez E, Gregory PD, Liu Q, Holmes MC, Cannon PM, Zaia JA, DiGiusto DL (2013) Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases. Mol Ther 21:1259–1269CrossRefPubMedCentralPubMedGoogle Scholar
  45. Liu J, Gaj T, Patterson JT, Sirk SJ, Barbas CF 3rd (2014) Cell-penetrating peptide-mediated delivery of TALEN proteins via bioconjugation for genome engineering. PLoS ONE 9:e85755CrossRefPubMedCentralPubMedGoogle Scholar
  46. Lombardo A, Genovese P, Beausejour CM, Colleoni S, Lee YL, Kim KA, Ando D, Urnov FD, Galli C, Gregory PD, Holmes MC, Naldini L (2007) Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat Biotechnol 25:1298–1306CrossRefPubMedGoogle Scholar
  47. Lombardo A, Cesana D, Genovese P, Di Stefano B, Provasi E, Colombo DF, Neri M, Magnani Z, Cantore A, Lo Riso P, Damo M, Pello OM, Holmes MC, Gregory PD, Gritti A, Broccoli V, Bonini C, Naldini L (2011) Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat Methods 8:861–869CrossRefPubMedGoogle Scholar
  48. Maier DA, Brennan AL, Jiang S, Binder-Scholl GK, Lee G, Plesa G, Zheng Z, Cotte J, Carpenito C, Wood T, Spratt SK, Ando D, Gregory P, Holmes MC, Perez EE, Riley JL, Carroll RG, June CH, Levine BL (2013) Efficient clinical scale gene modification via zinc finger nuclease-targeted disruption of the HIV co-receptor CCR5. Hum Gene Ther 24:245–258CrossRefPubMedCentralPubMedGoogle Scholar
  49. Mali P, Aach J, Stranges PB, Esvelt KM, Moosburner M, Kosuri S, Yang L, Church GM (2013a) CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat Biotechnol 31:833–838CrossRefPubMedGoogle Scholar
  50. Mali P, Esvelt KM, Church GM (2013b) Cas9 as a versatile tool for engineering biology. Nat Methods 10:957–963CrossRefPubMedCentralPubMedGoogle Scholar
  51. Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM (2013c) RNA-guided human genome engineering via Cas9. Science 339:823–826CrossRefPubMedCentralPubMedGoogle Scholar
  52. Mani M, Kandavelou K, Dy FJ, Durai S, Chandrasegaran S (2005) Design, engineering, and characterization of zinc finger nucleases. Biochem Biophys Res Commun 335:447–457CrossRefPubMedGoogle Scholar
  53. Manjunath N, Yi G, Dang Y, Shankar P (2013) Newer gene editing technologies toward HIV gene therapy. Viruses 5:2748–2766CrossRefPubMedCentralPubMedGoogle Scholar
  54. Manson McManamy ME, Hakre S, Verdin EM, Margolis DM (2014) Therapy for latent HIV-1 infection: the role of histone deacetylase inhibitors. Antivir Chem Chemother 23:145–149CrossRefPubMedGoogle Scholar
  55. Mariyanna L, Priyadarshini P, Hofmann-Sieber H, Krepstakies M, Walz N, Grundhoff A, Buchholz F, Hildt E, Hauber J (2012) Excision of HIV-1 proviral DNA by recombinant cell permeable tre-recombinase. PLoS ONE 7:e31576CrossRefPubMedCentralPubMedGoogle Scholar
  56. Matalon S, Rasmussen TA, Dinarello CA (2011) Histone deacetylase inhibitors for purging HIV-1 from the latent reservoir. Mol Med 17:466–472CrossRefPubMedCentralPubMedGoogle Scholar
  57. Mussolino C, Morbitzer R, Lutge F, Dannemann N, Lahaye T, Cathomen T (2011) A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res 39:9283–9293CrossRefPubMedCentralPubMedGoogle Scholar
  58. Mussolino C, Alzubi J, Fine EJ, Morbitzer R, Cradick TJ, Lahaye T, Bao G, Cathomen T (2014) TALENs facilitate targeted genome editing in human cells with high specificity and low cytotoxicity. Nucleic Acids Res 42:6762–6773CrossRefPubMedCentralPubMedGoogle Scholar
  59. Nerys-Junior A, Costa LC, Braga-Dias LP, Oliveira M, Rossi AD, da Cunha RD, Goncalves GS, Tanuri A (2014) Use of the heteroduplex mobility assay and cell sorting to select genome sequences of the CCR5 gene in HEK 293 T cells edited by transcription activator-like effector nucleases. Genet Mol Biol 37:120–126CrossRefPubMedCentralPubMedGoogle Scholar
  60. Niu J, Zhang B, Chen H (2014) Applications of TALENs and CRISPR/Cas9 in human cells and their potentials for gene therapy. Mol BiotechnolGoogle Scholar
  61. Pattanayak V, Lin S, Guilinger JP, Ma E, Doudna JA, Liu DR (2013) High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat Biotechnol 31:839–843CrossRefPubMedCentralPubMedGoogle Scholar
  62. Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA, Liu O, Wang N, Lee G, Bartsevich VV, Lee YL, Guschin DY, Rupniewski I, Waite AJ, Carpenito C, Carroll RG, Orange JS, Urnov FD, Rebar EJ, Ando D, Gregory PD, Riley JL, Holmes MC, June CH (2008) Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol 26:808–816CrossRefPubMedCentralPubMedGoogle Scholar
  63. Pingoud A, Silva GH (2007) Precision genome surgery. Nat Biotechnol 25:743–744CrossRefPubMedGoogle Scholar
  64. Platt RJ, Chen S, Zhou Y, Yim MJ, Swiech L, Kempton HR, Dahlman JE, Parnas O, Eisenhaure TM, Jovanovic M, Graham DB, Jhunjhunwala S, Heidenreich M, Xavier RJ, Langer R, Anderson DG, Hacohen N, Regev A, Feng G, Sharp PA, Zhang F (2014) CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell 159:440–455CrossRefPubMedGoogle Scholar
  65. Qu X, Wang P, Ding D, Li L, Wang H, Ma L, Zhou X, Liu S, Lin S, Wang X, Zhang G, Liu S, Liu L, Wang J, Zhang F, Lu D, Zhu H (2013) Zinc-finger-nucleases mediate specific and efficient excision of HIV-1 proviral DNA from infected and latently infected human T cells. Nucleic Acids Res 41:7771–7782CrossRefPubMedCentralPubMedGoogle Scholar
  66. Qu X, Wang P, Ding D, Wang X, Zhang G, Zhou X, Liu L, Zhu X, Zeng H, Zhu H (2014) Zinc finger nuclease: a new approach for excising HIV-1 proviral DNA from infected human T cells. Mol Biol Rep 41:5819–5827CrossRefPubMedGoogle Scholar
  67. Ramalingam S, Annaluru N, Kandavelou K, Chandrasegaran S (2014) TALEN-mediated generation and genetic correction of disease-specific human induced pluripotent stem cells. Curr Gene TherGoogle Scholar
  68. Ran FA, Hsu PD, Lin CY, Gootenberg JS, Konermann S, Trevino AE, Scott DA, Inoue A, Matoba S, Zhang Y, Zhang F (2013) Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154:1380–1389CrossRefPubMedGoogle Scholar
  69. Rasmussen TA, Schmeltz Sogaard O, Brinkmann C, Wightman F, Lewin SR, Melchjorsen J, Dinarello C, Ostergaard L, Tolstrup M (2013) Comparison of HDAC inhibitors in clinical development: effect on HIV production in latently infected cells and T-cell activation. Hum Vaccin Immunother 9:993–1001CrossRefPubMedCentralPubMedGoogle Scholar
  70. Sander JD, Joung JK (2014) CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol 32:347–355CrossRefPubMedCentralPubMedGoogle Scholar
  71. Sapranauskas R, Gasiunas G, Fremaux C, Barrangou R, Horvath P, Siksnys V (2011) The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli. Nucleic Acids Res 39:9275–9282CrossRefPubMedCentralPubMedGoogle Scholar
  72. Schiffer JT, Aubert M, Weber ND, Mintzer E, Stone D, Jerome KR (2012) Targeted DNA mutagenesis for the cure of chronic viral infections. J Virol 86:8920–8936CrossRefPubMedCentralPubMedGoogle Scholar
  73. Shan L, Siliciano RF (2013) From reactivation of latent HIV-1 to elimination of the latent reservoir: the presence of multiple barriers to viral eradication. Bioessays 35:544–552CrossRefPubMedCentralPubMedGoogle Scholar
  74. Shen B, Zhang W, Zhang J, Zhou J, Wang J, Chen L, Wang L, Hodgkins A, Iyer V, Huang X, Skarnes WC (2014) Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects. Nat Methods 11:399–402CrossRefPubMedGoogle Scholar
  75. Siliciano RF, Greene WC (2011) HIV latency. Cold Spring Harb Perspect Med 1:a007096CrossRefPubMedCentralPubMedGoogle Scholar
  76. Siliciano JD, Siliciano RF (2014) Recent developments in the search for a cure for HIV-1 infection: targeting the latent reservoir for HIV-1. J Allergy Clin Immunol 134:12–19CrossRefPubMedGoogle Scholar
  77. Smith C, Gore A, Yan W, Abalde-Atristain L, Li Z, He C, Wang Y, Brodsky RA, Zhang K, Cheng L, Ye Z (2014) Whole-genome sequencing analysis reveals high specificity of CRISPR/Cas9 and TALEN-based genome editing in human iPSCs. Cell Stem Cell 15:12–13CrossRefPubMedCentralPubMedGoogle Scholar
  78. Stone D, Kiem HP, Jerome KR (2013) Targeted gene disruption to cure HIV. Curr Opin HIV AIDS 8:217–223CrossRefPubMedCentralPubMedGoogle Scholar
  79. Suenaga T, Kohyama M, Hirayasu K, Arase H (2014) Engineering large viral DNA genomes using the CRISPR-Cas9 system. Microbiol Immunol 58:513–522CrossRefPubMedGoogle Scholar
  80. Tang C, Zhang Q, Li X, Fan N, Yang Y, Quan L, Lai L (2014) Targeted modification of CCR5 gene in rabbits by TALEN. Yi Chuan 36:360–368PubMedGoogle Scholar
  81. Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH (2014) Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 370:901–910CrossRefPubMedCentralPubMedGoogle Scholar
  82. Tsai SQ, Wyvekens N, Khayter C, Foden JA, Thapar V, Reyon D, Goodwin MJ, Aryee MJ, Joung JK (2014) Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat Biotechnol 32:569–576CrossRefPubMedCentralPubMedGoogle Scholar
  83. van der Kuyl AC (2012) HIV infection and HERV expression: a review. Retrovirology 9:6CrossRefPubMedCentralPubMedGoogle Scholar
  84. Van Lint C, Bouchat S, Marcello A (2013) HIV-1 transcription and latency: an update. Retrovirology 10:67CrossRefPubMedCentralPubMedGoogle Scholar
  85. Veres A, Gosis BS, Ding Q, Collins R, Ragavendran A, Brand H, Erdin S, Talkowski ME, Musunuru K (2014) Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing. Cell Stem Cell 15:27–30CrossRefPubMedGoogle Scholar
  86. Voit RA, McMahon MA, Sawyer SL, Porteus MH (2013) Generation of an HIV resistant T-cell line by targeted “stacking” of restriction factors. Mol Ther 21:786–795CrossRefPubMedCentralPubMedGoogle Scholar
  87. Wang J, Quake SR (2014) RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection. Proc Natl Acad Sci U S A 111:13157–13162CrossRefPubMedCentralPubMedGoogle Scholar
  88. Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R (2013) One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153:910–918CrossRefPubMedCentralPubMedGoogle Scholar
  89. Wayengera M (2011) Proviral HIV-genome-wide and pol-gene specific zinc finger nucleases: usability for targeted HIV gene therapy. Theor Biol Med Model 8:26CrossRefPubMedCentralPubMedGoogle Scholar
  90. Wilen CB, Wang J, Tilton JC, Miller JC, Kim KA, Rebar EJ, Sherrill-Mix SA, Patro SC, Secreto AJ, Jordan AP, Lee G, Kahn J, Aye PP, Bunnell BA, Lackner AA, Hoxie JA, Danet-Desnoyers GA, Bushman FD, Riley JL, Gregory PD, June CH, Holmes MC, Doms RW (2011) Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases. PLoS Pathog 7:e1002020CrossRefPubMedCentralPubMedGoogle Scholar
  91. Wu Y, Liang D, Wang Y, Bai M, Tang W, Bao S, Yan Z, Li D, Li J (2013) Correction of a genetic disease in mouse via use of CRISPR-Cas9. Cell Stem Cell 13:659–662CrossRefPubMedGoogle Scholar
  92. Xiao A, Cheng Z, Kong L, Zhu Z, Lin S, Gao G, Zhang B (2014) CasOT: a genome-wide Cas9/gRNA off-target searching tool. BioinformaticsGoogle Scholar
  93. Xie S, Shen B, Zhang C, Huang X, Zhang Y (2014) sgRNAcas9: a software package for designing CRISPR sgRNA and evaluating potential off-target cleavage sites. PLoS ONE 9:e100448CrossRefPubMedCentralPubMedGoogle Scholar
  94. Yang L, Guell M, Byrne S, Yang JL, De Los AA, Mali P, Aach J, Kim-Kiselak C, Briggs AW, Rios X, Huang PY, Daley G, Church G (2013) Optimization of scarless human stem cell genome editing. Nucleic Acids Res 41:9049–9061CrossRefPubMedCentralPubMedGoogle Scholar
  95. Yao Y, Nashun B, Zhou T, Qin L, Qin L, Zhao S, Xu J, Esteban MA, Chen X (2012) Generation of CD34+ cells from CCR5-disrupted human embryonic and induced pluripotent stem cells. Hum Gene Ther 23:238–242CrossRefPubMedGoogle Scholar
  96. Ye L, Wang J, Beyer AI, Teque F, Cradick TJ, Qi Z, Chang JC, Bao G, Muench MO, Yu J, Levy JA, Kan YW (2014) Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Delta32 mutation confers resistance to HIV infection. Proc Natl Acad Sci U S A 111:9591–9596CrossRefPubMedCentralPubMedGoogle Scholar
  97. Yi G, Choi JG, Bharaj P, Abraham S, Dang Y, Kafri T, Alozie O, Manjunath MN, Shankar P (2014) CCR5 gene editing of resting CD4(+) T cells by transient ZFN expression from HIV envelope pseudotyped nonintegrating lentivirus confers HIV-1 resistance in humanized mice. Mol Ther Nucleic Acids 3:e198CrossRefPubMedCentralPubMedGoogle Scholar
  98. Yuan J, Wang J, Crain K, Fearns C, Kim KA, Hua KL, Gregory PD, Holmes MC, Torbett BE (2012) Zinc-finger nuclease editing of human cxcr4 promotes HIV-1 CD4(+) T cell resistance and enrichment. Mol Ther 20:849–859CrossRefPubMedCentralPubMedGoogle Scholar
  99. Zhang F, Wen Y, Guo X (2014) CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum Mol GenetGoogle Scholar
  100. Zhen S, Hua L, Takahashi Y, Narita S, Liu YH, Li Y (2014) In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by CRISPR/Cas9. Biochem Biophys Res Commun 450:1422–1426CrossRefPubMedGoogle Scholar
  101. Zhou Y, Zhu S, Cai C, Yuan P, Li C, Huang Y, Wei W (2014) High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells. Nature 509:487–491CrossRefPubMedGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2015

Authors and Affiliations

  1. 1.Department of Neuroscience, Center for Neurovirology and the Comprehensive NeuroAIDS CenterTemple University School of MedicinePhiladelphiaUSA

Personalised recommendations