Fight fire with fire: Gene therapy strategies to cure HIV

References

• UNAIDS. AIDS by the numbers, AIDS is not over, but it can be. 2016. DOI:10.1038/scientificamerican0615-17
   Google Scholar
• Chun T-W, Moir S, Fauci AS. HIV reservoirs as obstacles and opportunities for an HIV cure. Nat Immunol. 2015;16:584–589.
   PubMed Web of Science ®Google Scholar
• Phillips AN, Neaton J, Lundgren JD. The role of HIV in serious diseases other than AIDS. AIDS. 2008;22:2409–2418.
   PubMed Web of Science ®Google Scholar
• Hasse B, Ledergerber B, Furrer H, et al. Morbidity and aging in hiv-infected persons: the swiss HIV cohort study. CID. 2011;53:1131–1139.
   Web of Science ®Google Scholar
• Sanjuán R, Nebot MR, Chirico N, et al. Viral Mutation Rates. J Virol. 2010;84:9733–9748.
   PubMed Web of Science ®Google Scholar
• Cuevas JM, Geller R, Garijo R, et al. Extremely high mutation rate of HIV-1 in vivo. PLoS Biol. 2015;13:1–19.
   Web of Science ®Google Scholar
• Lloyd SB, Kent SJ, Winnall WR. The high cost of fidelity. AIDS Res Hum Retroviruses. 2014;30:8–16.
   PubMed Web of Science ®Google Scholar
• Deeks SG. HIV: shock and kill. Nature. 2012;487:439–440.
   PubMed Web of Science ®Google Scholar
• Chomont N, El-Far M, Ancuta P, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009;15:893–900.
   PubMed Web of Science ®Google Scholar
• Buzon MJ, Sun H, Li C, et al. HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat Med. 2014;20:139–142.
   PubMed Web of Science ®Google Scholar
• Perreau M, Schiavo E, Heyer V, et al. Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J Exp Med. 2013;210:143–156.
   PubMed Web of Science ®Google Scholar
• Maldarelli F, Wu X, Su L, et al. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells. Science (80-.). 2014;345:179–183.
   PubMed Web of Science ®Google Scholar
• Wagner TA, McLaughlin S, Garg K, et al. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science (80-.). 2014;345:570–573.
   PubMed Web of Science ®Google Scholar
• Barton K, Winckelmann A, Palmer S. HIV-1 reservoirs during suppressive therapy. Trends Microbiol. 2016;24:345–355.
   PubMed Web of Science ®Google Scholar
• Darcis G, Van Driessche B, Van Lint C. Preclinical shock strategies to reactivate latent HIV-1: an update. Curr Opin HIV AIDS. 2016;11:388–393.
   PubMed Web of Science ®Google Scholar
• Van Lint C, Bouchat S, Marcello A. HIV-1 transcription and latency: an update. Retrovirology. 2013;10:67.
   PubMed Web of Science ®Google Scholar
• Darcis G, Kula A, Bouchat S, et al. An in-depth comparison of latency-reversing agent combinations in various in vitro and Ex Vivo HIV-1 latency models identified bryostatin-1+JQ1 and ingenol-B+JQ1 to potently reactivate viral gene expression. PLoS Pathog. 2015;11:e1005063.
   PubMed Web of Science ®Google Scholar
• Archin NM, Boyer L, Morantte I, et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012;489:460–460.
   Web of Science ®Google Scholar
• Elliott JH, Wightman F, Solomon A, et al. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog. 2014;10:e1004473.
   PubMed Web of Science ®Google Scholar
• Rasmussen TA, Tolstrup M, Brinkmann CR, 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 Web of Science ®Google Scholar
• Deeks SG, Kitchen CM, Liu L, et al. Immune activation set point during early HIV infection predicts subsequent CD4 + T-cell changes independent of viral load. Blood 2004;104:942–947.
   Google Scholar
• Giorgi JV, Hultin L, McKeating J, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis. 1999;179:859–870.
   PubMed Web of Science ®Google Scholar
• Shan L, Deng K, Schroff NS, et al. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity. 2012;36:491–501.
   PubMed Web of Science ®Google Scholar
• Appay V, Nixon DF, Donahoe SM, et al. specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function. J Exp Med. 2000;192:63–75.
   PubMed Web of Science ®Google Scholar
• Hütter G, Nowak D, Mossner M, et al. Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation. N Engl J Med. 2009;360:692–698.
   PubMed Web of Science ®Google Scholar
• Allers K, Hutter G, Hofmann J, et al. Evidence for the cure of HIV infection by CCR5 Δ32/Δ32 stem cell transplantation. Blood. 2011;117:2791–2799.
   PubMed Web of Science ®Google Scholar
• Unseld M, Marienfeld JR, Brandt P, et al. Global distribution of the CCR5 gene 32-basepair deletion. Nat Genet. 1997;15:57–61.
   PubMed Web of Science ®Google Scholar
• Su B, Sun G, Lu D, et al. Distribution of three HIV-1 resistance-conferring polymorphisms (SDF1-3’A, CCR2-641, and CCR5-delta32) in global populations. Eur J Hum Genet. 2000;8:975–979.
   PubMed Web of Science ®Google Scholar
• Novembre J, Galvani AP, Slatkin M. The geographic spread of the CCR5 Δ32 HIV-resistance allele. PLoS Biol. 2005;3:1954–1962.
   Web of Science ®Google Scholar
• Pavletic ZS, Arrowsmith ER, Bierman PJ, et al. Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia. Bone Marrow Transplant. 2000;25:717–722.
   PubMed Web of Science ®Google Scholar
• Sobecks RM, Leis JF, Gale RP, et al. Outcomes of human leukocyte antigen-matched sibling donor hematopoietic cell transplantation in chronic lymphocytic leukemia: myeloablative versus reduced-intensity conditioning regimens. Biol Blood Marrow Transplant. 2014;20:1390–1398.
   PubMed Web of Science ®Google Scholar
• Doney KC, Chauncey T, Appelbaum FR, et al. Allogeneic related donor hematopoietic stem cell transplantation for treatment of chronic lymphocytic leukemia. Bone Marrow Transpl. 2002;29:817–823.
   PubMed Web of Science ®Google Scholar
• Toze CL, Shepherd JD, Connors JM, et al. Allogeneic bone marrow transplantation for low-grade lymphoma and chronic lymphocytic leukemia. Bone Marrow Transplant. 2000;25:605–612.
   PubMed Web of Science ®Google Scholar
• Pavletich NP, Pabo CO. Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science (80-.). 1991;252:809–817.
   PubMed Web of Science ®Google Scholar
• Urnov FD, Rebar EJ, Holmes MC, et al. Genome editing with engineered zinc finger nucleases. Nat Rev Genet. 2010;11:636–646.
   PubMed Web of Science ®Google Scholar
• Yao Y, Nashun B, Zhou T, et al. Generation of CD34+ cells from CCR5-disrupted human embryonic and induced pluripotent stem cells. Hum Gene Ther. 2012;23:238–242.
   PubMed Web of Science ®Google Scholar
• Perez EE, Wang J, Miller JC, et al. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol. 2008;26:808–816.
   PubMed Web of Science ®Google Scholar
• Li L, Krymskaya L, Wang J, et al. Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases. Mol Ther. 2013;21:1259–1269.
   PubMed Web of Science ®Google Scholar
• Holt N, Wang J, Kim K, et al. Zinc finger nuclease-mediated CCR5 knockout hematopoietic stem cell transplantation controls HIV-1 in vivo. Nat Biotechnol. 2010;28:839–847.
   PubMed Web of Science ®Google Scholar
• Koppensteiner H, Wu L. Macrophages and their relevance in Human Immunodeficiency Virus Type I infection. Retrovirology. 2012;9:82.
   PubMed Web of Science ®Google Scholar
• Wu L, KewalRamani VN. Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol. 2006;6:859–868.
   PubMed Web of Science ®Google Scholar
• Tebas P, Stein D, Tang WW, et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med. 2014;370:901–910.
   PubMed Web of Science ®Google Scholar
• Mussolino C, Morbitzer R, Lütge F, et al. A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res. 2011;39:9283–9293.
   PubMed Web of Science ®Google Scholar
• Ye L, Wang J, Beyer AI, 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 U S A. 2014;111:9591–9596.
   PubMed Web of Science ®Google Scholar
• Cho SW, Kim S, Kim JM, et al. Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol. 2013;31:230–232.
   PubMed Web of Science ®Google Scholar
• Shepherd JC, Jacobson L, Qiao W, et al. Emergence and persistence of CXCR4-tropic HIV-1 in a population of men from the multicenter AIDS cohort study. J Infect Dis. 2008;198:1104–1112.
   PubMed Web of Science ®Google Scholar
• Daar ES, Kesler KL, Petropoulos CJ, et al. Baseline HIV type 1 coreceptor tropism predicts disease progression. Clin Infect Dis. 2007;45:643–649.
   PubMed Web of Science ®Google Scholar
• Peled A, Petit I, Kollet O, et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science. 1999;283:845–848.
   PubMed Web of Science ®Google Scholar
• Wilen CB, Wang J, Tilton JC, et al. Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases. PLoS Pathog. 2011;7:e1002020.
   PubMed Web of Science ®Google Scholar
• Yuan J, Wang J, Crain K, et al. Zinc-finger nuclease editing of human cxcr4 promotes HIV-1 CD4+ T cell resistance and enrichment. Mol Ther. 2012;20:849–859.
   PubMed Web of Science ®Google Scholar
• Didigu CA, Wilen CB, Wang J, et al. Simultaneous zinc- finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4 1 T cells from HIV-1 infection. Blood. 2014;123:61–69.
   PubMed Web of Science ®Google Scholar
• Voit RA, McMahon MA, Sawyer SL, et al. Generation of an HIV resistant T-cell line by targeted ‘stacking’ of restriction factors. Mol Ther. 2013;21:786–795.
   PubMed Web of Science ®Google Scholar
• Sarkar I, Hauber I, Hauber J, et al. HIV-1 Proviral DNA excision using an evolved recombinase. Science (80-.). 2007;316:1912–1915.
   PubMed Web of Science ®Google Scholar
• Hauber I, Hofmann-Sieber H, Chemnitz J, et al. Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. PLoS Pathog. 2013;9:e1003587.
   PubMed Web of Science ®Google Scholar
• Karpinski J, Chemnitz J, Hauber I, et al. Universal Tre (uTre) recombinase specifically targets the majority of HIV-1 isolates. J Int AIDS Soc. 2014;17:19706.
   PubMed Web of Science ®Google Scholar
• Qu X, Wang P, Ding D. et al. Zinc-finger-nucleases mediate specific and efficient excision of HIV-1 proviral DNA from infected and latently infected human T cells. Nucleic Acids Res. 2013;41:7771–7782.
   Google Scholar
• Ebina H, Misawa N, Kanemura Y, et al. Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus. Sci Rep. 2013;3:2510.
   PubMed Web of Science ®Google Scholar
• Hu W, Kaminski R, Yang F, et al. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. Proc Natl Acad Sci U S. 2014;111:11461–11466.
   PubMed Web of Science ®Google Scholar
• Zhu W, Lei R, Le Duff Y, et al. The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA. Retrovirology. 2015;12:22.
   PubMed Web of Science ®Google Scholar
• Ebina H, Kanemura Y, Misawa N, et al. A high excision potential of TALENs for integrated DNA of HIV-based lentiviral vector. PLoS One. 2015;10:1–15.
   Web of Science ®Google Scholar
• Aubert M, Ryu BY, Banks L, et al. Successful targeting and disruption of an integrated reporter lentivirus using the engineered homing endonuclease Y2 I-AniI. PLoS One. 2011;6:e16825.
   Web of Science ®Google Scholar
• Kaminski R, Chen Y, Fischer T, et al. Elimination of HIV-1 genomes from human T-lymphoid cells by CRISPR/Cas9 gene editing. Sci Rep. 2016;6:22555.
   PubMed Web of Science ®Google Scholar
• Kaminski R, Bella R, Yin C, et al. Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study. Gene Ther. 23, 690–695 (2016).
   Google Scholar
• Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science (80-.). 2015;348:62–68.
   PubMed Web of Science ®Google Scholar
• Restifo N, Dudley M, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2012;12:269–281.
   PubMed Web of Science ®Google Scholar
• Fesnak AD, June CH, Levine BL. Engineered T cells: the promise and challenges of cancer immunotherapy. Nat Rev Cancer. 2016;16:566–581.
   PubMed Web of Science ®Google Scholar
• Roberts MR, Qin L, Zhang D, et al. Targeting of Human Immunodeficiency Virus-Infected Cells by CD8+ T Lymphocytes Armed With Universal T-cell Receptors. Blood 84, 2878–2889 (1994).
   Google Scholar
• Tran AC, Zhang D, Byrn R, et al. Chimeric zeta-receptors direct human natural killer (NK) effector function to permit killing of NK-resistant tumor cells and HIV-infected T lymphocytes. J Immunol. 1995;155:1000–1009.
   PubMed Web of Science ®Google Scholar
• Riddell S, Elliott M, Lewinsohn DA, et al. T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nat Med. 1996;2:216–223.
   PubMed Web of Science ®Google Scholar
• Mitsuyasu RT, Anton PA, Deeks SG, et al. Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency virus-infected subjects. Blood. 2000;96:785–793.
   PubMed Web of Science ®Google Scholar
• Walker RE, Bechtel CM, Natarajan V, et al. Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood. 2000;96:467–474.
   PubMed Web of Science ®Google Scholar
• Deeks SG, Wagner B, Anton PA, et al. A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy. Mol Ther. 2002;5:788–797.
   PubMed Web of Science ®Google Scholar
• June CH, Levine BL. T cell engineering as therapy for cancer and HIV: our synthetic future. Philos Trans R Soc Lond B Biol Sci. 2015;370:20140374.
   PubMed Web of Science ®Google Scholar
• Huang J, Kang B, Ishida E, et al. Identification of a CD4-binding-site antibody to HIV that evolved near-pan neutralization breadth. Immunity. 2016;45:1108–1121.
   PubMed Web of Science ®Google Scholar
• Kwong PD, Mascola JR, Nabel GJ. Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nat Rev Immunol. 2013;13:693–701.
   PubMed Web of Science ®Google Scholar
• Mascola JR, Lewis MG, Stiegler G, et al. Protection of Macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J Virol. 1999;73:4009–4018.
   PubMed Web of Science ®Google Scholar
• Mascola JR, Stiegler G, VanCott TC, et al. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med. 2000;6:207–210.
   PubMed Web of Science ®Google Scholar
• Parren PW, Marx PA, Hessell AJ, et al. Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J Virol. 2001;75:8340–8347.
   PubMed Web of Science ®Google Scholar
• Hessell AJ, Poignard P, Hunter M, et al. EFFECTIVE, LOW TITER, ANTIBODY PROTECTION AGAINST LOW-DOSE REPEATED MUCOSAL SHIV CHALLENGE IN. Nat Med. 2009;15:951–954.
   PubMed Web of Science ®Google Scholar
• Hessell AJ, Rakasz EG, Tehrani DM, et al. Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. J Virol. 2010;84:1302–1313.
   PubMed Web of Science ®Google Scholar
• Ng CT, Jaworski JP, Jayaraman P, et al. Passive neutralizing antibody controls SHIV viremia and enhances B cell responses in infant macaques. Nat Med. 2010;16:1117–1119.
   Google Scholar
• Horwitz JA, Halper-Stromberg A, Mouquet H, et al. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. Proc Natl Acad Sci U S. 2013;110:16538–16543.
   PubMed Web of Science ®Google Scholar
• Shingai M, Nishimura Y, Klein F, et al. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature. 2013;503:277–280.
   PubMed Web of Science ®Google Scholar
• Barouch DH, Whitney JB, Moldt B, et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature. 2013;503:224–228.
   PubMed Web of Science ®Google Scholar
• Lynch RM, Boritz E, Coates EE, et al. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci Transl Med. 2015;7.
   Google Scholar
• Caskey M, Klein F, Lorenzi JCC, et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature. 2015;522:487–491.
   PubMed Web of Science ®Google Scholar
• Bar KJ, Sneller MC, Harrison LJ, et al. Effect of HIV antibody VRC01 on viral rebound after treatment interruption. N Engl J Med. 2016;375:2037–2050. NEJMoa1608243. DOI:10.1056/NEJMoa1608243
   PubMed Web of Science ®Google Scholar
• Scheid JF, Horwitz JA, Bar-On Y, et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016;535:556–560.
   PubMed Web of Science ®Google Scholar
• Byrareddy SN, Arthos J, Cicala C, et al. Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy. Science (80-). 2016;354:197 LP–202.
   Web of Science ®Google Scholar
• Bakker JM, Bleeker WK, Parren PWHI. Therapeutic antibody gene transfer: an active approach to passive immunity. Mol Ther. 2004;10:411–416.
   PubMed Web of Science ®Google Scholar
• Lewis AD, Chen R, Montefiori DC, et al. Generation of neutralizing activity against human immunodeficiency virus type 1 in serum by antibody gene transfer. J Virol. 2002;76:8769–8775.
   PubMed Web of Science ®Google Scholar
• Balazs AB, Chen J, Hong CM, et al. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature. 2011;481:81–84.
   PubMed Web of Science ®Google Scholar
• Saunders KO, Wang L, Joyce MG, et al. Broadly neutralizing human immunodeficiency virus type 1 antibody gene transfer protects non-human primates from mucosal simian-human immunodeficiency virus infection. J Virol. 2015;89:8334–8345.
   PubMed Web of Science ®Google Scholar
• Varela-Rohena A, Molloy PE, Dunn SM, et al. Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor. Nat Med. 2008;14:1390–1395.
   PubMed Web of Science ®Google Scholar
• Joseph A, Lindqvist B, Garoff H. Lentiviral Vectors Encoding Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Receptor Genes Efficiently Convert Peripheral Blood CD8 T Lymphocytes into Cytotoxic T Lymphocytes with Potent In Vitro and In Vivo HIV-1-Specific Inhibitory Activity. J Virol. 2008;82:3078–3089.
   PubMed Web of Science ®Google Scholar
• Linette GP, Wittamer V, Bertrand JY, et al. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood. 2013;122:863–871.
   PubMed Web of Science ®Google Scholar
• Cameron BJ, Gerry AB, Dukes J, et al. Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Sci Transl Med. 2013;5:197ra103.
   PubMed Web of Science ®Google Scholar
• Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3:388–398.
   PubMed Web of Science ®Google Scholar
• Sadelain M, Brentjens R, Rivière I. The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol. 2009;21:215–223.
   PubMed Web of Science ®Google Scholar
• Schwartz O, Maréchal V, Le Gall S, et al. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med. 1996;2:338–342.
   PubMed Web of Science ®Google Scholar
• Collins KL, Chen BK, Kalams SA, et al. HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature. 1998;391:397–401.
   PubMed Web of Science ®Google Scholar
• Maus MV, Grupp SA, Porter DL, et al. Antibody-modified T cells : cARs take the front seat for hematologic malignancies. Blood. 2014;123:2625–2635.
   PubMed Web of Science ®Google Scholar
• Maude SL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–1517.
   PubMed Web of Science ®Google Scholar
• Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–528.
   PubMed Web of Science ®Google Scholar
• Scholler J, Brady TL, Binder-Scholl G, et al. Decade-long safety and function of retroviral-modified chimeric antigen receptor T-cells. Sci Translational Med. 2012;4:132ra53-132ra53.
   PubMed Web of Science ®Google Scholar
• Kamata M, Ansaloni A, Pedersen JF, et al. Ectopic expression of anti-HIV-1 shRNAs protects CD8(+) T cells modified with CD4zeta CAR from HIV-1 infection and alleviates impairment of cell proliferation. Biochem Biophys Res Commun. 2015;463:216–221.
   PubMed Web of Science ®Google Scholar
• Zhen A, Kamata M, Rezek V, et al. HIV-specific immunity derived from chimeric antigen receptor-engineered stem cells. Mol Ther. 2015;23:1358–1367.
   PubMed Web of Science ®Google Scholar
• Liu B, Zou F, Lu L, et al. Chimeric Antigen Receptor T Cells Guided by the Single-Chain Fv of a Broadly Neutralizing Antibody Specifically and Effectively Eradicate Virus Reactivated from Latency in CD4+ T Lymphocytes Isolated from HIV-1-Infected Individuals Receiving Suppressive C. J Virol. 2016;90:9712–9724.
   PubMed Web of Science ®Google Scholar
• Ali A, Kitchen SG, Chen ISY, et al. HIV-1-specific chimeric antigen receptors based on broadly-neutralizing antibodies. J Virol. 2016;90:JVI.00805-16.
   PubMed Web of Science ®Google Scholar
• Hale M, Luli S, Sabater L, et al. Engineering HIV-resistant, anti-HIV chimeric antigen receptor T cells. Mol Ther. 2017;25:1–10.
   PubMed Web of Science ®Google Scholar
• Zhou T, Georgiev I, Wu X, et al. Structural basis for broad and potent neutralization ofHIV-1 byAntibody VRC01. Science (80-.). 2010;329:811–817.
   PubMed Web of Science ®Google Scholar
• Wu X, Yang Z-Y, Li Y, et al. Rational design of envelope identifies broadly neutralizinghuman monoclonal antibodies to HIV-1. Science (80-.). 2010;329:856–861.
   PubMed Web of Science ®Google Scholar
• Stein S, Ott MG, Schultze-Strasser S, et al. Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat Med. 2010;16:198–204.
   PubMed Web of Science ®Google Scholar
• Hacein-Bey Abina S, Schirger A. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2003;348:255–256.
   PubMed Web of Science ®Google Scholar
• Hacein-Bey-Abina S, Von Kalle C, Schmidt M, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science (80-.). 2003;302:415–419.
   PubMed Web of Science ®Google Scholar
• Cartier N, Hacein-Bey-Abina S, Bartholomae CC, et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science (80-.). 2009;326:818–823.
   PubMed Web of Science ®Google Scholar
• Moehle EA, Rock JM, Lee Y-L, et al. Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases (vol 104, pg 3055, 2007). Proc Natl Acad Sci U S. 2007;104:6090.
   Web of Science ®Google Scholar
• Zou J, Sweeney CL, Chou B-K, et al. Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells : functional correction by zinc finger nuclease – mediated safe harbor targeting. Blood. 2011;117:5561–5572.
   PubMed Web of Science ®Google Scholar
• Lombardo A, Cesana D, Genovese P, et al. Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat Methods. 2011;8:861–869.
   PubMed Web of Science ®Google Scholar
• Almasbak H, Aarvak T, Vemuri MC. CAR T cell therapy: a game changer in cancer treatment. J Immunol Res. 2016;5474602:2016.
   Google Scholar