Current application of CRISPR/Cas9 gene-editing technique to eradication of HIV/AIDS

Abstract

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) remains a major health hazard despite significant advances in prevention and treatment of HIV infection. The major reason for the persistence of HIV/AIDS is the inability of existing treatments to clear or eradicate the multiple HIV reservoirs that exist in the human body. To suppress the virus replication and rebound, HIV/AIDS patients must take life-long antiviral medications. The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system is an emerging gene-editing technique with the potential to eliminate or disrupt HIV-integrated genomes or HIV-infected cells from multiple HIV reservoirs, which could result in the complete cure of HIV/AIDS. Encouraging progress has already been reported for the application of the CRISPR/Cas9 technique to HIV/AIDS treatment and prevention, both in vitro in human patient cells and in vivo in animal model experiments. In this review, we will summarize the most recent progress in the application of the CRISPR/Cas9 gene-editing technique to HIV/AIDS therapy and elimination. Future directions and trends of such applications are also discussed.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4

References

  1. 1

    Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 1997; 387: 183–188.

    CAS  PubMed  Article  Google Scholar 

  2. 2

    Chun TW, Engel D, Mizell SB, Ehler LA, Fauci AS . Induction of HIV-1 replication in latently infected CD4+ T cells using a combination of cytokines. J Exp Med 1998; 188: 83–91.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. 3

    Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 1997; 278: 1295–1300.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4

    Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nature Medicine 2003; 9: 727–728.

    CAS  PubMed  Article  Google Scholar 

  5. 5

    Bagasra O, Lavi E, Bobroski L, Khalili K, Pestaner JP, Tawadros R et al. Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS 1996; 10: 573–585.

    CAS  PubMed  Article  Google Scholar 

  6. 6

    Fischer-Smith T, Croul S, Sverstiuk AE, Capini C, L'Heureux D, Regulier EG et al. CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J Neurovirol 2001; 7: 528–541.

    CAS  PubMed  Article  Google Scholar 

  7. 7

    Petito CK, Chen H, Mastri AR, Torres-Munoz J, Roberts B, Wood C . HIV infection of choroid plexus in AIDS and asymptomatic HIV-infected patients suggests that the choroid plexus may be a reservoir of productive infection. J Neurovirol 1999; 5: 670–677.

    CAS  PubMed  Article  Google Scholar 

  8. 8

    McElrath MJ, Steinman RM, Cohn ZA . Latent HIV-1 infection in enriched populations of blood monocytes and T cells from seropositive patients. J Clin Invest 1991; 87: 27–30.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. 9

    Chun TW, Engel D, Berrey MM, Shea T, Corey L, Fauci AS . Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection. Proc Natl Acad Sci USA 1998; 95: 8869–8873.

    CAS  PubMed  Article  Google Scholar 

  10. 10

    Chun TW, Nickle DC, Justement JS, Meyers JH, Roby G, Hallahan CW et al. Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis 2008; 197: 714–720.

    CAS  PubMed  Article  Google Scholar 

  11. 11

    Smith PD, Meng G, Salazar-Gonzalez JF, Shaw GM . Macrophage HIV-1 infection and the gastrointestinal tract reservoir. J Leuko Biol 2003; 74: 642–649.

    CAS  PubMed  Article  Google Scholar 

  12. 12

    Lambert-Niclot S, Peytavin G, Duvivier C, Poirot C, Algarte-Genin M, Pakianather S et al. Low frequency of intermittent HIV-1 semen excretion in patients treated with darunavir-ritonavir at 600/100 milligrams twice a day plus two nucleoside reverse transcriptase inhibitors or monotherapy. Antimicrob Agents Chemother 2010; 54: 4910–4913.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. 13

    Cu-Uvin S, DeLong AK, Venkatesh KK, Hogan JW, Ingersoll J, Kurpewski J et al. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS 2010; 24: 2489–2497.

    PubMed  Article  Google Scholar 

  14. 14

    Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 2009; 15: 893–900.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15

    Chun TW, Nickle DC, Justement JS, Large D, Semerjian A, Curlin ME et al. HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir. J Clin Invest 2005; 115: 3250–3255.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16

    Fletcher CV, Staskus K, Wietgrefe SW, Rothenberger M, Reilly C, Chipman JG et al. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci USA 2014; 111: 2307–2312.

    CAS  PubMed  Article  Google Scholar 

  17. 17

    Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC et al. Validation of the CNS Penetration-Effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 2008; 65: 65–70.

    PubMed  PubMed Central  Article  Google Scholar 

  18. 18

    Solas C, Lafeuillade A, Halfon P, Chadapaud S, Hittinger G, Lacarelle B . Discrepancies between protease inhibitor concentrations and viral load in reservoirs and sanctuary sites in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 2003; 47: 238–243.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19

    Heaton RK, Clifford DB, Franklin DR Jr., Woods SP, Ake C, Vaida F et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 2010; 75: 2087–2096.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20

    Heaton RK, Franklin DR Jr, Deutsch R, Letendre S, Ellis RJ, Casaletto K et al. Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study. Clin Infect Dis 2015; 60: 473–480.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  21. 21

    Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 2007; 69: 1789–1799.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22

    Churchill MJ, Wesselingh SL, Cowley D, Pardo CA, McArthur JC, Brew BJ et al. Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann Neurol 2009; 66: 253–258.

    PubMed  Article  PubMed Central  Google Scholar 

  23. 23

    Ellis RJ, Rosario D, Clifford DB, McArthur JC, Simpson D, Alexander T et al. Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER Study. Arch Neurol 2010; 67: 552–558.

    PubMed  PubMed Central  Article  Google Scholar 

  24. 24

    Churchill MJ, Gorry PR, Cowley D, Lal L, Sonza S, Purcell DF et al. Use of laser capture microdissection to detect integrated HIV-1 DNA in macrophages and astrocytes from autopsy brain tissues. J Neurovirol 2006; 12: 146–152.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  25. 25

    Narasipura SD, Kim S, Al-Harthi L . Epigenetic regulation of HIV-1 latency in astrocytes. J Virol 2014; 88: 3031–3038.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  26. 26

    Nath A . Eradication of human immunodeficiency virus from brain reservoirs. J Neurovirol 2015; 21: 227–234.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  27. 27

    Dampier W, Nonnemacher MR, Sullivan NT, Jacobson JM, Wigdahl B . HIV excision utilizing crispr/cas9 technology: attacking the proviral quasispecies in reservoirs to achieve a cure. MOJ Immunol 2014; 1: pii:00022.

    Google Scholar 

  28. 28

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

    PubMed  PubMed Central  Article  Google Scholar 

  29. 29

    Hu W, Kaminski R, Yang F, Zhang Y, Cosentino L, Li F et al. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. Proc Natl Acad Sci USA 2014; 111: 11461–11466.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  30. 30

    Kaminski R, Chen Y, Fischer T, Tedaldi E, Napoli A, Zhang Y et al. Elimination of HIV-1 genomes from human T-lymphoid cells by CRISPR/Cas9 gene editing. Sci Rep 2016; 6: 22555.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31

    Saayman SM, Lazar DC, Scott TA, Hart JR, Takahashi M, Burnett JC et al. Potent and targeted activation of latent HIV-1 using the CRISPR/dCas9 activator complex. Mol Ther 2016; 24: 488–498.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32

    Zhang Y, Yin C, Zhang T, Li F, Yang W, Kaminski R et al. CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoirs. Sci Rep 2015; 5: 16277.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33

    Chylinski K, Le Rhun A, Charpentier E . The tracrRNA and Cas9 families of type II CRISPR-Cas immunity systems. RNA Biol 2013; 10: 726–737.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34

    Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E . A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012; 337: 816–821.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35

    Chavez L, Calvanese V, Verdin E . HIV latency is established directly and early in both resting and activated primary CD4 T cells. PLoS Pathog 2015; 11: e1004955.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  36. 36

    Stanley SK, Ostrowski MA, Justement JS, Gantt K, Hedayati S, Mannix M et al. Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type 1. N Engl J Med 1996; 334: 1222–1230.

    CAS  PubMed  Article  Google Scholar 

  37. 37

    Brady T, Agosto LM, Malani N, Berry CC, O'Doherty U, Bushman F . HIV integration site distributions in resting and activated CD4+ T cells infected in culture. AIDS 2009; 23: 1461–1471.

    PubMed  PubMed Central  Article  Google Scholar 

  38. 38

    Schneider M, Tigges B, Meggendorfer M, Helfer M, Ziegenhain C, Brack-Werner R . A new model for post-integration latency in macroglial cells to study HIV-1 reservoirs of the brain. AIDS 2015; 29: 1147–1159.

    CAS  PubMed  Article  Google Scholar 

  39. 39

    Sunshine S, Kirchner R, Amr SS, Mansur L, Shakhbatyan R, Kim M et al. HIV Integration site analysis of cellular models of HIV latency with a probe-enriched next-generation sequencing assay. J Virol 2016; 90: 4511–4519.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40

    du Chene I, Basyuk E, Lin YL, Triboulet R, Knezevich A, Chable-Bessia C et al. Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency. EMBO J 2007; 26: 424–435.

    CAS  PubMed  Article  Google Scholar 

  41. 41

    Gallastegui E, Millan-Zambrano G, Terme JM, Chavez S, Jordan A . Chromatin reassembly factors are involved in transcriptional interference promoting HIV latency. J Virol 2011; 85: 3187–3202.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. 42

    Barboric M, Nissen RM, Kanazawa S, Jabrane-Ferrat N, Peterlin BM . NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol Cell 2001; 8: 327–337.

    CAS  PubMed  Article  Google Scholar 

  43. 43

    Lenasi T, Contreras X, Peterlin BM . Transcriptional interference antagonizes proviral gene expression to promote HIV latency. Cell Host Microbe 2008; 4: 123–133.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. 44

    Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H et al. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med 2007; 13: 1241–1247.

    CAS  PubMed  Article  Google Scholar 

  45. 45

    Patel P, Ansari MY, Bapat S, Thakar M, Gangakhedkar R, Jameel S . The microRNA miR-29a is associated with human immunodeficiency virus latency. Retrovirology 2014; 11: 108.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  46. 46

    Ruelas DS, Chan JK, Oh E, Heidersbach AJ, Hebbeler AM, Chavez L et al. MicroRNA-155 Reinforces HIV Latency. J Biol Chem 2015; 290: 13736–13748.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47

    Delagreverie HM, Delaugerre C, Lewin SR, Deeks SG, Li JZ . Ongoing clinical trials of human immunodeficiency virus latency-reversing and immunomodulatory agents. open forum. Infect Dis 2016; 3: ofw189.

    Google Scholar 

  48. 48

    Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 2012; 487: 482–485.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49

    Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon A et al. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV 2014; 1: e13–e21.

    PubMed  Article  Google Scholar 

  50. 50

    Porteus MH, Baltimore D . Chimeric nucleases stimulate gene targeting in human cells. Science 2003; 300: 763.

    PubMed  PubMed Central  Article  Google Scholar 

  51. 51

    Miller JC, Holmes MC, Wang J, Guschin DY, Lee YL, Rupniewski I et al. An improved zinc-finger nuclease architecture for highly specific genome editing. Nat Biotechnol 2007; 25: 778–785.

    CAS  PubMed  Article  Google Scholar 

  52. 52

    Wood AJ, Lo TW, Zeitler B, Pickle CS, Ralston EJ, Lee AH et al. Targeted genome editing across species using ZFNs and TALENs. Science 2011; 333: 307.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. 53

    Miller JC, Tan S, Qiao G, Barlow KA, Wang J, Xia DF et al. A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 2011; 29: 143–148.

    CAS  PubMed  Article  Google Scholar 

  54. 54

    Zhang F, Cong L, Lodato S, Kosuri S, Church GM, Arlotta P . Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. Nat Biotechnol 2011; 29: 149–153.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  55. 55

    Reyon D, Tsai SQ, Khayter C, Foden JA, Sander JD, Joung JK . FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 2012; 30: 460–465.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. 56

    Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 2007; 315: 1709–1712.

    CAS  Article  Google Scholar 

  57. 57

    Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N et al. Multiplex genome engineering using CRISPR/Cas systems. Science 2013; 339: 819–823.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. 58

    Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE et al. RNA-guided human genome engineering via Cas9. Science 2013; 339: 823–826.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. 59

    Hsu PD, Lander ES, Zhang F . Development and applications of CRISPR-Cas9 for genome engineering. Cell 2014; 157: 1262–1278.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  60. 60

    Shi B, Li J, Shi X, Jia W, Wen Y, Hu X et al. TALEN-mediated knockout of CCR5 confers protection against infection of human immunodeficiency virus. J Acquir Immune Defic Syndr 2016.

  61. 61

    Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 2014; 370: 901–910.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  62. 62

    Maier DA, Brennan AL, Jiang S, Binder-Scholl GK, Lee G, Plesa G et al. Efficient clinical scale gene modification via zinc finger nuclease-targeted disruption of the HIV co-receptor CCR5. Hum Gene Ther 2013; 24: 245–258.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  63. 63

    Strong CL, Guerra HP, Mathew KR, Roy N, Simpson LR, Schiller MR . Damaging the Integrated HIV Proviral DNA with TALENs. PloS One 2015; 10: e0125652.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  64. 64

    Anders C, Niewoehner O, Duerst A, Jinek M . Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease. Nature 2014; 513: 569–573.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. 65

    Jinek M, Jiang F, Taylor DW, Sternberg SH, Kaya E, Ma E et al. Structures of Cas9 endonucleases reveal RNA-mediated conformational activation. Science 2014; 343: 1247997.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  66. 66

    Nishimasu H, Ran FA, Hsu PD, Konermann S, Shehata SI, Dohmae N et al. Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 2014; 156: 935–949.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. 67

    Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F . Genome engineering using the CRISPR-Cas9 system. Nat Protoc 2013; 8: 2281–2308.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  68. 68

    Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, Barcena C et al. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 2015; 517: 583–588.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. 69

    Hou P, Chen S, Wang S, Yu X, Chen Y, Jiang M et al. Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection. Sci Rep 2015; 5: 15577.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. 70

    Schumann K, Lin S, Boyer E, Simeonov DR, Subramaniam M, Gate RE et al. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. Proc Natl Acad Sci USA 2015; 112: 10437–10442.

    CAS  PubMed  Article  Google Scholar 

  71. 71

    Ye L, Wang J, Beyer AI, Teque F, Cradick TJ, Qi Z et al. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Delta32 mutation confers resistance to HIV infection. Proc Natl Acad Sci USA 2014; 111: 9591–9596.

    CAS  PubMed  Article  Google Scholar 

  72. 72

    Wang W, Ye C, Liu J, Zhang D, Kimata JT, Zhou P . CCR5 gene disruption via lentiviral vectors expressing Cas9 and single guided RNA renders cells resistant to HIV-1 infection. PloS One 2014; 9: e115987.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  73. 73

    Li C, Guan X, Du T, Jin W, Wu B, Liu Y et al. Inhibition of HIV-1 infection of primary CD4+ T-cells by gene editing of CCR5 using adenovirus-delivered CRISPR/Cas9. J Gen Virol 2015; 96: 2381–2393.

    CAS  PubMed  Article  Google Scholar 

  74. 74

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

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  75. 75

    Kaminski R, Bella R, Yin C, Otte J, Ferrante P, Gendelman HE et al. Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study. Gene Ther 2016; 23: 696.

    CAS  PubMed  Article  Google Scholar 

  76. 76

    Wang G, Zhao N, Berkhout B, Das AT . CRISPR-Cas9 can inhibit HIV-1 replication but NHEJ repair facilitates virus escape. Mol Ther 2016; 24: 522–526.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  77. 77

    Wang Z, Pan Q, Gendron P, Zhu W, Guo F, Cen S et al. CRISPR/Cas9-derived mutations both inhibit HIV-1 replication and accelerate viral escape. Cell Rep 2016; 15: 481–489.

    CAS  PubMed  Article  Google Scholar 

  78. 78

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. 79

    Heckl D, Kowalczyk MS, Yudovich D, Belizaire R, Puram RV, McConkey ME et al. Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing. Nat Biotechnol 2014; 32: 941–946.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  80. 80

    Platt RJ, Chen S, Zhou Y, Yim MJ, Swiech L, Kempton HR et al. CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell 2014; 159: 440–455.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. 81

    Mansouri M, Bellon-Echeverria I, Rizk A, Ehsaei Z, Cianciolo Cosentino C, Silva CS et al. Highly efficient baculovirus-mediated multigene delivery in primary cells. Nat Commun 2016; 7: 11529.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. 82

    Zuckermann M, Hovestadt V, Knobbe-Thomsen CB, Zapatka M, Northcott PA, Schramm K et al. Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling. Nat Commun 2015; 6: 7391.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  83. 83

    Wang L, Hao Y, Li H, Zhao Y, Meng D, Li D et al. Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles. J Drug Target 2015; 23: 832–846.

    CAS  PubMed  Article  Google Scholar 

  84. 84

    Wang M, Zuris JA, Meng F, Rees H, Sun S, Deng P et al. Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles. Proc Natl Acad Sci USA 2016; 113: 2868–2873.

    CAS  PubMed  Article  Google Scholar 

  85. 85

    Qazi S, Miettinen HM, Wilkinson RA, McCoy K, Douglas T, Wiedenheft B . Programmed self-assembly of an active P22-Cas9 nanocarrier system. Mol Pharm 2016; 13: 1191–1196.

    CAS  PubMed  Article  Google Scholar 

  86. 86

    Sun W, Ji W, Hall JM, Hu Q, Wang C, Beisel CL et al. Self-assembled DNA nanoclews for the efficient delivery of CRISPR-Cas9 for genome editing. Angew Chem Int Ed Engl 2015; 54: 12029–12033.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  87. 87

    Yin H, Song CQ, Dorkin JR, Zhu LJ, Li Y, Wu Q et al. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol 2016; 34: 328–333.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  88. 88

    Bickel U, Kang YS, Yoshikawa T, Pardridge WM . In vivo demonstration of subcellular localization of anti-transferrin receptor monoclonal antibody-colloidal gold conjugate in brain capillary endothelium. J Histochem Cytochem 1994; 42: 1493–1497.

    CAS  PubMed  Article  Google Scholar 

  89. 89

    Yoshikawa T, Pardridge WM . Biotin delivery to brain with a covalent conjugate of avidin and a monoclonal antibody to the transferrin receptor. J Pharmacol Exp Ther 1992; 263: 897–903.

    CAS  PubMed  Google Scholar 

  90. 90

    Zhang Y, Boado RJ, Pardridge WM . In vivo knockdown of gene expression in brain cancer with intravenous RNAi in adult rats. J Gene Med 2003; 5: 1039–1045.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  91. 91

    Clark AJ, Davis ME . Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core. Proc Natl Acad Sci USA 2015; 112: 12486–12491.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  92. 92

    Ding H, Sagar V, Agudelo M, Pilakka-Kanthikeel S, Atluri VS, Raymond A et al. Enhanced blood-brain barrier transmigration using a novel transferrin embedded fluorescent magneto-liposome nanoformulation. Nanotechnology 2014; 25: 055101.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  93. 93

    De Luca MA, Lai F, Corrias F, Caboni P, Bimpisidis Z, Maccioni E et al. Lactoferrin- and antitransferrin-modified liposomes for brain targeting of the NK3 receptor agonist senktide: preparation and in vivo evaluation. Int J Pharm 2015; 479: 129–137.

    CAS  PubMed  Article  Google Scholar 

  94. 94

    Tomitaka A, Arami H, Gandhi S, Krishnan KM . Lactoferrin conjugated iron oxide nanoparticles for targeting brain glioma cells in magnetic particle imaging. Nanoscale 2015; 7: 16890–16898.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  95. 95

    Fornaguera C, Dols-Perez A, Caldero G, Garcia-Celma MJ, Camarasa J, Solans C . PLGA nanoparticles prepared by nano-emulsion templating using low-energy methods as efficient nanocarriers for drug delivery across the blood-brain barrier. J Control Release 2015; 211: 134–143.

    CAS  PubMed  Article  Google Scholar 

  96. 96

    Huang Y, Zhang B, Xie S, Yang B, Xu Q, Tan J et al. Modified with Tween 80 pass through the intact blood-brain barrier in rats under magnetic field. ACS Appl Mater Interfaces 2016; 8: 11336–11341.

    CAS  PubMed  Article  Google Scholar 

  97. 97

    Kaushik A, Jayant RD, Nikkhah-Moshaie R, Bhardwaj V, Roy U, Huang Z et al. Magnetically guided central nervous system delivery and toxicity evaluation of magneto-electric nanocarriers. Sci Rep 2016; 6: 25309.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  98. 98

    Nair M, Guduru R, Liang P, Hong J, Sagar V, Khizroev S . Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers. Nat Commun 2013; 4: 1707.

    PubMed  Article  CAS  Google Scholar 

  99. 99

    Sagar V, Pilakka-Kanthikeel S, Atluri VS, Ding H, Arias AY, Jayant RD et al. Therapeutical neurotargeting via magnetic nanocarrier: implications to opiate-induced neuropathogenesis and neuroAIDS. J Biomed Nanotechnol 2015; 11: 1722–1733.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  100. 100

    Jayant RD, Atluri VS, Agudelo M, Sagar V, Kaushik A, Nair M . Sustained-release nanoART formulation for the treatment of neuroAIDS. Int J Nanomed 2015; 10: 1077–1093.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported by grants (R01DA037838 and R01DA034547) from National Institutes of Health, US. We also thank Maureen Pelham and Courtney Myhr for their help in English editing.

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Z Huang or M Nair.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Huang, Z., Tomitaka, A., Raymond, A. et al. Current application of CRISPR/Cas9 gene-editing technique to eradication of HIV/AIDS. Gene Ther 24, 377–384 (2017). https://doi.org/10.1038/gt.2017.35

Download citation

Further reading