Novel cell and gene therapies for HIV

Cold Spring Harbor Perspectives in Medicine

Volumn 2, Issue 10, 2012, Pages

  Hoxie, James A ^a   June, Carl H ^b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APTAMER; CHEMOKINE RECEPTOR CCR5; COMPLEMENTARY RNA; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; NUCLEIC ACID SYNTHESIS INHIBITOR; PROTEIN INHIBITOR; RIBOZYME; TRIPARTITE MOTIF PROTEIN 5; VIRUS VECTOR;

ACUTE GRANULOCYTIC LEUKEMIA; ALLOTRANSPLANTATION; ARTICLE; AUTOPSY; CELL THERAPY; DNA END JOINING REPAIR; GENE DELETION; GENE EXPRESSION; GENE TARGETING; GENE THERAPY; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME; LONG TERMINAL REPEAT; POLYMERASE CHAIN REACTION; RNA INTERFERENCE; SEVERE COMBINED IMMUNODEFICIENCY; SURVIVAL; VIRUS LATENCY; VIRUS REPLICATION; XENOTRANSPLANTATION; GENETICS; METHODOLOGY; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; REVIEW;

HUMAN IMMUNODEFICIENCY VIRUS 1;

BASE SEQUENCE; GENE TARGETING; GENETIC THERAPY; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HIV INFECTIONS; HUMANS; MOLECULAR SEQUENCE DATA; RECEPTORS, CCR5; VIRUS LATENCY;

EID: 84880872115     PISSN: None     EISSN: 21571422     Source Type: Journal    
DOI: 10.1101/cshperspect.a007179     Document Type: Article

References (153)

1. Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T. 2010. Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation. Blood 117: 2791-2799.
2. + hematopoietic progenitor cells transduced with an anti-HIV ribozyme. Human Gene Ther 10: 2255-2270.
3. Amado RG, Mitsuyasu RT, Rosenblatt JD, Ngok FK, Bakker A, Cole S, Chorn N, Lin LS, Bristol G, Boyd MP, et al. 2004. Anti-human immunodeficiency virus hematopoietic progenitor cell-delivered ribozyme in a phase I study: Myeloid and lymphoid reconstitution in human immunodeficiency virus type-1-infected patients. Hum Gene Ther 15: 251-262.
4. An DS, Donahue RE, Kamata M, Poon B, Metzger M, Mao SH, Bonifacino A, Krouse AE, Darlix JL, Baltimore D, et al. 2007. Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates. Proc Natl Acad Sci 104: 13110-13115.
5. Anderson WF. 1984. Prospects for human gene therapy. Science 226: 401-409.
6. Anderson J, Akkina R. 2005. HIV-1 resistance conferred by siRNA cosuppression of CXCR 4 and CCR 5 coreceptors by a bispecific lentiviral vector. AIDS Res Theory 2: 1-12.
7. Anderson J, Banerjea A, Akkina R. 2003. Bispecific short hairpin siRNA constructs targeted to CD4, CXCR4, and CCR5 confer HIV-1 resistance. Oligonucleotides 13: 303-312.
8. Anderson JS, Walker J, Nolta JA, Bauer G. 2009. Specific transduction of HIV-susceptible cells for CCR5 knockdown and resistance to HIV infection: A novel method for targeted gene therapy and intracellular immunization. J Acquir Immune Defic Syndr 52: 152-161.
9. Angelucci E, Lucarelli G, Baronciani D, Durazzi SM, Galimberti M, Maddaloni D, Polchi P. 1990. Bone marrow transplantation in an HIV positive thalassemic child following therapy with azidothymidine. Haematologica 75: 285-287.
10. Aronson N, Benstein W, Levine B, Jagodzinski L, Plesa G, Cox J, Darden J, PolonisV, Gibbs B, Flaks H, et al. 2008. A clinical trial of CD4 ζ gene-modified T cell infusion with and without IL-2 in HIV-infected participants. In AIDS 2008 XVII International AIDS Conference, 3-8 August 2008, Abstract TUPDA104, p. 328. Mexico City.
11. Arya SK, Guo C, Josephs SF, Wong-Staal F. 1985. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science 229: 69.
12. Avettand-Fenoel V, Mahlaoui N, Chaix ML, Milliancourt C, Burgard M, Cavazzana-Calvo M, Rouzioux C, Blanche S. 2007. Failure of bone marrow transplantation to eradicate HIV reservoir despite efficient HAART. AIDS 21: 776-777.
13. + hematopoietic progenitor cells in vitro and in a SCID-hu mouse model in vivo. Mol Ther 1: 244-254.
14. Bai J, Rossi J, Akkina R. 2001. Multivalent anti-CCR5 ribozymes for stem cell-based HIV type 1 gene therapy. AIDS Res Hum Retrov 17: 385-399.
15. + count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS 22: 841-848.
16. Baltimore D. 1988. Gene therapy. Intracellular immunization. Nature 335: 395-396.
17. Bardini G, Re MC, Rosti G, Belardinelli AR. 1991. HIV infection and bone-marrow transplantation. Lancet 337: 1163-1164.
18. Barrett A, Malkovska V. 1996. Graft-versus-leukaemia: Understanding and using the alloimmune response to treat haematological malignancies. Brit J Haematol 93: 754-761.
19. + cells from HIV-1-infected donors using retroviral vectors containing anti-HIV-1 genes. Blood 89: 2259-2267.
20. Beard BC, Trobridge GD, Ironside C, McCune JS, Adair JE, Kiem HP. 2010. Efficient and stable MGMT-mediated selection of long-term repopulating stem cells in nonhuman primates. J Clin Invest 120: 2345-2354.
21. Blankson JN, Persaud D, Siliciano RF. 2002. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med 53: 557-593.
22. Bohjanen PR, Liu Y, Garcia-Blanco MA. 1997. TAR RNA decoys inhibit tat-activated HIV-1 transcription after preinitiation complex formation. Nucleic Acids Res 25: 4481-4486.
23. Butler SL, Valdez H, Westby M, Perros M, June CH, Jacobson JM, Levy Y, CooperDA, Douek D, Lederman MM, Tebas P. 2011. Disease-modifying therapeutic concepts for HIV in the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr (in press).
24. Cannon P, June C. 2011. Chemokine receptor 5 knockout strategies. Curr Opin HIV AIDS 6: 74-79.
25. Carter CC, Onafuwa-Nuga A, McNamara LA, Riddell J IV., Bixby D, Savona MR, Collins KL. 2010. HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs. Nat Med 16: 446-451.
26. Cavazzana-Calvo M, Fischer A. 2007. Gene therapy for severe combined immunodeficiency: Are we there yet? J Clin Invest 117: 1456-1465.
27. Chatterjee S, Johnson PR, Wong KK Jr. 1992. Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus antisense vector. Science 258: 1485-1488.
28. Cheung MC, Pantanowitz L, Dezube BJ. 2005. AIDS-related malignancies: Emerging challenges in the era of highly active antiretroviral therapy. Oncologist 10: 412.
29. Chun TW, Fauci AS. 1999. Latent reservoirs of HIV: Obstacles to the eradication of virus. Proc Natl Acad Sci 96: 10958-10961.
30. Collman R, Shaheen F, Boyer J, Binder G, Zifchak L, Aberra F, McGarrity G, LevineB, Tebas P, June C, et al. 2009. Safety, antiviral effects, and quantitative measurement of modified CD4 T cells trafficking to gut lymphoid tissue in a phase I/II open-label clinical trial evaluating multiple infusions of lentiviral vector-modified CD4 T cells expressing long env antisense. In 16th Conference on Retroviruses and Opportunistic Infections Abstract #83, Feb 9, 2009. Montreal, Canada.
31. Cordelier P, Kulkowsky JW, Ko C, Matskevitch AA, McKee HJ, Rossi JJ, Bouhamdan M, Pomerantz RJ, Kari G, Strayer DS. 2004. Protecting from R5-tropic HIV: Individual and combined effectiveness of a hammerhead ribozyme and a single-chain Fv antibody that targets CCR5. Gene Ther 11: 1627-1637.
32. Deeks SG, McCune JM. 2010. Can HIV be cured with stem cell therapy? Nat Biotechnol 28: 807-810.
33. Deeks SG, Wagner B, Anton PA, Mitsuyasu RT, Scadden DT, Huang C, Macken C, Richman DD, Christopherson C, June CH, et al. 2002. A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination anti-retroviral therapy. Mol Ther 5: 788-797.
34. Denton P, Garcia J. 2009. Novel humanized murine models for HIV research. Curr HIV/AIDS Rep 6: 13-19.
35. + cells in patients undergoing transplantation for AIDS-related lymphoma. Sci Transl Med 2: 36-43.
36. Dropulic B, June CH. 2006. Gene-based immunotherapy for human immunodeficiency virus infection and acquired immunodeficiency syndrome. Hum Gene Ther 17: 577-588.
37. Dropulić B, Heermánková M, Pitha PM. 1996. A conditionally replicating HIV-1 vector interferes with wild-type HIV-1 replication and spread. Proc Natl Acad Sci 93: 11103-11108.
38. Edelstein ML, Abedi MR, Wixon J. 2007. Gene therapy clinical trials worldwide to 2007-An update. J Gene Med 9: 833-842.
39. Egelhofer M, Brandenburg G, Martinius H, Schult-Dietrich P, Melikyan G, Kunert R, Baum C, Choi I, Alexandrov A, von Laer D, et al. 2004. Inhibition of human immunodeficiency virus type 1 entry in cells expressing gp41-derived peptides. J Virol 78: 568-575.
40. Friedmann T. 1992. A brief history of gene therapy. Nat Genet 2: 93-98.
41. Friedmann T, Roblin R. 1972. Gene therapy for human genetic disease? Science 175: 949-955.
42. +T cell recovery with antiretroviral therapy: More than the sum of the parts. Clin Infect Dis 48: 362-364.
43. Giorgi JV, Hultin LE, McKeating JA, Johnson TD, Owens B, Jacobson LP, Shih R, Lewis J, Wiley DJ, Phair JP, et al. 1999. 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 179: 859-870.
44. Giri N, Vowels MR, Ziegler JB. 1992. Failure of allogeneic bone marrow transplantation to benefit HIV infection. J Paediatr Child Health 28: 331-333.
45. Gulick RM, Lalezari J, Goodrich J, Clumeck N, DeJesus E, Horban A, Nadler J, Clotet B, Karlsson A, Wohlfeiler M, et al. 2008. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med 359: 1429-1441.
46. Han Y, Wind-Rotolo M, Yang HC, Siliciano JD, Siliciano RF. 2007. Experimental approaches to the study of HIV-1 latency. Nat Rev Microbiol 5: 95-106.
47. Hannon G, Rossi J. 2004. Unlocking the potential of the human genome with RNA interference. Nature 431: 371-378.
48. Hassett J, Zaroulis C, Greenberg ML, Siegal FP, et al. 1983. Bone-marrow transplantation in AIDS. N Engl J Med 309: 665-665.
49. Hayakawa J, Washington K, Uchida N, Phang O, Kang EM, Hsieh MM, Tisdale JF. 2009. Long-term vector integration site analysis following retroviral mediated gene transfer to hematopoietic stem cells for the treatment of HIV infection. PLoS One 4: e4211. doi: 10. 1371/journal. pone. 0004211.
50. Held DM, Kissel JD, Patterson JT, Nickens DG, Burke DH. 2006. HIV-1 inactivation by nucleic acid aptamers. Front Biosci 11: 89-112.
51. Held DM, Kissel JD, Thacker SJ, Michalowski D, Saran D, Ji J, Hardy RW, RossiJJ, Burke DH. 2007. Cross-clade inhibition of recombinant human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus SIVcpz reverse transcriptases by RNA pseudoknot aptamers. J Virol 81: 5375-5384.
52. Hildinger M, Dittmar MT, Schult-Dietrich P, Fehse B, Schnierle BS, Thaler S, Stiegler G, Welker R, von Laer D. 2001. Membrane-anchored peptide inhibits human immunodeficiency virus entry. J Virol 75: 3038-3042.
53. Holland HK, Saral R, Rossi JJ, Donnenberg AD, Burns WH, Beschorner WE, Farzadegan H, Jones RJ, Quinnan GV, Vogelsang GB. 1989. Allogeneic bone marrow transplantation, zidovudine, and human immunodeficiency virus type 1 (HIV-1) infection. Studies in a patient with non-Hodgkin lymphoma. Ann Intern Med 111: 973-981.
54. Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, Crooks GM, Kohn DB, Gregory PD, Holmes MC, et al. 2010. Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. NatBiotechnol 28: 839-847.
55. Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K, et al. 1996. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med 2: 1240-1243.
56. Hutter G, Thiel E. 2011. Allogeneic transplantation of CCR5-deficient progenitor cells in a patient with HIV infection: An update after 3 years and the search for patient no. 2. AIDS 25: 273-274.
57. Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K, Schneider T, Hofmann J, Kücherer C, Blau O, et al. 2009. Long-term control of HIV by CCR5 Δ32/Δ32 stem-cell transplantation. N Engl J Med 360: 692-696.
58. Joshi PJ, Fisher TS, Prasad VR. 2003. Anti-HIV inhibitors based on nucleic acids: Emergence of aptamers as potent antivirals. Curr Drug Targets Infect Disord 3: 383-400.
59. June CH, Blazar BR, Riley JL. 2009. Engineering lymphocyte subsets: Tools, trials and tribulations. Nat Rev Immunol 9: 704-716.
60. Kamp C, Wolf T, Bravo IG, Kraus B, Krause B, Neumann B, Winskowsky G, Thielen A, Werner A, Schnierle BS. 2010. Decreased HIV diversity after allogeneic stem cell transplantation of an HIV-1 infected patient: A case report. Virol J 7: 55.
61. Kang EM, de Witte M, Malech H, Morgan RA, Phang S, Carter C, Leitman SF, Childs R, Barrett AJ, Little R, et al. 2002. Nonmyeloablative conditioning followed by transplantation of genetically modified HLA-matched peripheral blood progenitor cells for hematologic malignancies in patients with acquired immunodeficiency syndrome. Blood 99: 698-701.
62. Kaufmann GR, Zaunders JJ, Cunningham P, Kelleher AD, Grey P, Smith D, CarrA, Cooper DA. 2000. Rapid restoration of CD4 T cell subsets in subjects receiving antiretroviral therapy during primary HIV-1 infection. AIDS 14: 2643-2651.
63. + cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis 48: 787-794.
64. Kim SS, Peer D, Kumar P, Subramanya S, Wu H, Asthana D, Habiro K, Yang YG, Manjunath N, Shimaoka M, et al. 2009. RNAi-mediated CCR5 silencing by LFA-1-targeted nanoparticles prevents HIV infection in BLT mice. Mol Ther 18: 370-376.
65. + T cells expressing a membrane-bound fusion inhibitor following HIV-1 infection. PLoS One 5: 378-384.
66. Kissel JD, Held DM, Hardy RW, Burke DH. 2007. Active site binding and sequence requirements for inhibition of HIV-1 reverse transcriptase by the RT1 family of single-stranded DNA aptamers. Nucleic Acids Res 35: 5039-5050.
67. Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, HoggRS, Deeks SG, Eron JJ, Brooks JT, et al. 2009. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 360: 1815-1826.
68. + cells from the bone marrow of human immunodeficiency virus-1-infected children. Blood 94: 368-371.
69. Kumar P, Ban HS, Kim SS, Wu H, Pearson T, Greiner DL, Laouar A, Yao J, HaridasV, Habiro K, et al. 2008. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 134: 577-586.
70. Lane HC, Masur H, Longo DL, Klein HG, Rook AH, Quinnan GV Jr., Steis RG, Macher A, Whalen G, Edgar LC. 1984. Partial immune reconstitution in a patient with the acquired immunodeficiency syndrome. N Engl J Med 311: 1099-1103.
71. Lares MR, Rossi JJ, Ouellet DL. 2010. RNAi and small interfering RNAs in human disease therapeutic applications. Trends Biotechnol 28: 570-579.
72. Leavitt MC, Yu M, Yamada O, Kraus G, Looney D, Poeschla E, Wong-Staal F. 1994. Transfer of an anti-HIV-1 ribozyme gene into primary human lymphocytes. Hum Gene Ther 5: 1115-1120.
73. Lee SW, Gallardo HF, Gilboa E, Smith C. 1994. Inhibition of human immunodeficiency virus type 1 in human T cells by a potent Rev response element decoy consisting of the 13-nucleotide minimal Rev-binding domain. J Virol 68: 8254-8264.
74. Lee NS, Dohjima T, Bauer G, Li H, Li MJ, Ehsani A, Salvaterra P, Rossi J. 2002. Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol 20: 500-505.
75. Lekakis J, Ikonomidis I. 2010. Cardiovascular complications of AIDS. Curr Opin Crit Care 16: 408-412.
76. Levine BL, Humeau LM, Boyer J, MacGregor RR, Rebello T, Lu X, Binder GK, Slepushkin V, Lemiale F, Mascola JR, et al. 2006. Gene transfer in humans using a conditionally replicating lentiviral vector. Proc Natl Acad Sci 103: 17372-17377.
77. Lewden C, Salmon D, Morlat P, Bévilacqua S, Jougla E, Bonnet F, Héripret L, Costagliola D, May T, Chêne G. Mortality 2000 Study Group. 2005. Causes of death among human immunodeficiency virus (HIV)-infected adults in the era of potent antiretroviral therapy: emerging role of hepatitis and cancers, persistent role of AIDS. Int J Epidemiol 34: 121-130.
78. 3 on long-term combination antiretroviral therapy reach same mortality rates as the general population. J Acquir Immune Defic Syndr 46: 72-77.
79. Li MJ, Kim J, Li S, Zaia J, Yee JK, Anderson J, Akkina R, Rossi JJ. 2005. Long-term inhibition of HIV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme, and a nucleolar-localizing TAR decoy. Mol Ther 12: 900-909.
80. Liang M, Kamata M, Chen KN, Pariente N, An DS, Chen IS. 2010. Inhibition of HIV-1 infection by a unique short hairpin RNA to chemokine receptor 5 delivered into macrophages through hematopoietic progenitor cell transduction. J Gene Med 12: 255-265.
81. Lisziewicz J, Sun D, Smythe J, Lusso P, Lori F, Louie A, Markham P, Rossi J, Reitz M, Gallo RC. 1993. Inhibition of human immunodeficiency virus type 1 replication by regulated expression of a polymeric Tat activation response RNA decoy as a strategy for gene therapy in AIDS. Proc Natl Acad Sci 90: 8000-8004.
82. Lo AS, Zhu Q, Marasco WA. 2008. Intracellular antibodies (intrabodies) and their therapeutic potential. In Therapeutic antibodies (ed. Chernajovsky Y, Nissim A), Vol. 181, pp. 343-373. Springer-Verlag, Berlin.
83. Lobato M, Rabbitts T. 2004. Intracellular antibodies as specific reagents for functional ablation: Future therapeutic molecules. Curr Mol Med 4: 519-528.
84. Lohse N, Hansen AB, Pedersen G, Kronborg G, Gerstoft J, Sørensen HT, VaethM, Obel N. 2007. Survival of persons with and without HIV infection in Denmark, 1995-2005. Ann Intern Med 146: 87-95.
85. Lombardo A, Genovese P, Beausejour CM, Colleoni S, Lee YL, Kim KA, Ando D, Urnov FD, Galli C, Gregory PD, et al. 2007. Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat Biotechnol 25: 1298-1306.
86. Lu X, Yu Q, Binder GK, Chen Z, Slepushkina T, Rossi J, Dropulic B. 2004. Antisense-mediated inhibition of human immunodeficiency virus (HIV) replication by use of an HIV type 1-based vector results in severely attenuated mutants incapable of developing resistance. J Virol 78: 7079-7088.
87. Maartens G, Boulle A, Mocroft A, Phillips AN, Gatell J, Ledergerber B, Fisher M, Clumeck N, Losso M, Lazzarin A, et al. 2007. Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: An observational cohort study. Commentary. Lancet 370: 407-413.
88. + T-lymphocytes in HIV-infected patients. J. Gene Med 7: 552-564.
89. Malim MH, Bieniasz PD. 2011. HIV restriction factors and mechanisms of evasion. Cold Spring Harb Pespect Med doi: 10. 1101/cshperspect. a006940.
90. Malim MH, Freimuth WW, Liu J, Boyle TJ, Lyerly HK, Cullen BR, Nabel GJ, et al. 1992. Stable expression of transdominant Rev protein in human T cells inhibits human immunodeficiency virus replication. J Exp Med 176: 1197-1201.
91. Mátrai JM, Chuah MK, VandenDriessche T. 2010. Recent advances in lentiviral vector development and applications. Mol Ther 18: 477-490.
92. McSweeney P, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, MaloneyDG, Chauncey TR, Gooley TA, Hegenbart U, Nash RA, et al. 2001. Hematopoietic cell transplantation in older patients with hematologic malignancies: Replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 97: 3390-3400.
93. Michaels MG, Kaufman C, Volberding PA, Gupta P, Switzer WM, Heneine W, Sandstrom P, Kaplan L, Swift P, Damon L, et al. 2004. Baboon bone-marrow xenotransplant in a patient with advanced HIV disease: Case report and 8-year follow-up. Transplantation 78: 1582-1589.
94. Michienzi A, Castanotto D, Lee N, LI S, Zaia JA, Rossi JJ. 2003. RNA-mediated inhibition of HIV in a gene therapy setting. Ann NY Acad Sci 1002: 63-71.
95. + cells. Nat Med 15: 285-292.
96. Milsom MD, Williams DA. 2007. Live and let die: In vivo selection of gene-modified hematopoietic stem cells via MGMT-mediated chemoprotection. DNA Repair 6: 1210-1221.
97. + T cells in human immunodeficiency virus-infected subjects. Blood 96: 785-793.
98. Montini E, Cesana D, Schmidt M, Sanvito F, Bartholomae CC, Ranzani M, Benedicenti F, Sergi Sergi L, Ambrosi A, Ponzoni M, et al. 2009. The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. J Clin Invest 119: 964-975.
99. Moore R, Keruly J, Gebo K, Lucas G. 2005. An improvement in virologic response to highly active antiretroviral therapy in clinical practice from 1996 through 2002. J Acquir Immune Defic Syndr 39: 195-198.
100. + T lymphocytes engineered with anti-human immunodeficiency virus (HIV) genes in HIV-infected individuals. Hum Gene Ther 16: 1065-1074.
101. Nazari R, Joshi S. 2008. CCR5 as target for HIV-1 gene therapy. Curr Gene Ther 8: 264-272.
102. Newrzela S, Cornils K, Li Z, Baum C, Brugman MH, Hartmann M, Meyer J, Hartmann S, Hansmann ML, Fehse B, et al. 2008. Resistance of mature T cells to oncogene transformation. Blood 112: 2278-2286.
103. Ngok FK, Mitsuyasu RT, Macpherson JL, Boyd MP, Symonds GP, Amado RG. 2004. Clinical gene therapy research utilizing ribozymes: Application to the treatment of HIV/AIDS. Methods Mol Biol 252: 581-598.
104. Nimjee SM, Rusconi CP, Sullenger BA. 2005. Aptamers: An emerging class of therapeutics. Medicine 56: 555-583.
105. Nisole S, Stoye JP, Saïb A. 2005. TRIM family proteins: Retroviral restriction and antiviral defence. Nat Rev Microbiol 3: 799-808.
106. Nunez M. 2010. Clinical syndromes and consequences of antiretroviral-related hepatotoxicity. Hepatology 52: 1143-1155.
107. Perez EE, Riley JL, Carroll RG, von Laer D, June CH. 2005. Suppression of HIV-1 infection in primary CD4 T cells transduced with a self-inactivating lentiviral vector encoding a membrane expressed gp41-derived fusion inhibitor. Clin Immunol 115: 26-32.
108. + T cells by genome editing using zinc-finger nucleases. Nat Biotechnol 26: 808-816.
109. + cells. Mol Ther 12: 77-86.
110. Polizzotto MN, Skinner M, Cole-Sinclair MF, Opat SS, Spencer A, Avery S. 2010. Allo-SCT for hematological malignancies in the setting of HIV. Bone Marrow Transpl 45: 584-586.
111. Poluri A, van Maanen M, Sutton RE. 2003. Genetic therapy for HIV/AIDS. Expert Opin Biol Ther 3: 951-963.
112. Qin XF, An DS, Chen IS, Baltimore D. 2003. Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci 100: 183-188.
113. Ranga U, Woffendin C, Verma S, Xu L, June CH, Bishop DK, Nabel GJ. 1998. Retroviral delivery of an antiviral gene in HIV-infected individuals. Proc Natl Acad Sci 95: 1201-1206.
114. Rebellato LM, Gross U, Verbanac KM, Thomas JM. 1994. A comprehensive definition of the major antibody specificities in polyclonal rabbit antithymocyte globulin. Transplantation 57: 685-694.
115. Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. 2009. The challenge of finding a cure for HIV infection. Science 323: 1304-1307.
116. Rodger AJ, Fox Z, Lundgren JD, Kuller LH, Boesecke C, Gey D, Skoutelis A, Goetz MB, Phillips AN. INSIGHT Strategies for Management of Antiretroviral Therapy (SMART) Study Group. 2009. Activation and coagulation biomarkers are independent predictors for the development of opportunistic disease in patients with HIV infection. J Infect Dis 200: 973-983.
117. Rossi JJ, June CH, Kohn DB, et al. 2007. Genetic therapies for HIV/AIDS. Nat Biotechnol 25: 1444-1454.
118. Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, et al. 1996. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene [see comments]. Nature 382: 722-725.
119. Sarver N, Cantin EM, Chang PS, Zaia JA, Ladne PA, Stephens DA, Rossi JJ. 1990. Ribozymes as potential anti-HIV-1 therapeutic agents. Science 247: 1222-1225.
120. Schackman BR, Gebo KA, Walensky RP, Losina E, Muccio T, Sax PE, WeinsteinMC, Seage GR III., Moore RD, Freedberg KA. 2006. The lifetime cost of current human immunodeficiency virus care in the United States. Med Care 44: 990-997.
121. Schlegel P, Beatty P, Halvorsen R, McCune J. 2000. Successful allogeneic bone marrow transplant in an HIV-1-positive man with chronic myelogenous leukemia. J Acquir Immune Defic Syndr 24: 289-290.
122. Schroers R, Davis CM, Wagner HJ, Chen SY. 2002. Lentiviral transduction of human T-lymphocytes with a RANTES intrakine inhibits human immunodeficiency virus type 1 infection. Gene Ther 9: 889-897.
123. Shimizu S, Hong P, Arumugam B, Pokomo L, Boyer J, Koizumi N, KittipongdajaP, Chen A, Bristol G, Galic Z, et al. 2010. A highly efficient short hairpin RNA potently down-regulates CCR5 expression in systemic lymphoid organs in the hu-BLT mouse model. Blood 115: 1534-1544.
124. Siliciano RF, Greene WC. 2011. HIV latency. Cold Spring Harb Perspect Med doi: 10. 1101/cshperspect. a007096.
125. Sodroski J, Rosen C, Goh WC, Haseltine W. 1985. A transcriptional activator protein encoded by the x-lor region of the human T-cell leukemia virus. Science 228: 1430.
126. + T cell precursor can develop into diverse effector and memory subsets. Immunity 27: 985-997.
127. Strayer DS, Akkina R, Bunnell BA, Dropulic B, Planelles V, Pomerantz RJ, RossiJJ, Zaia JA. 2005. Current status of gene therapy strategies to treat HIV/AIDS. Mol Ther 11: 823-842.
128. Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P, Sodroski J. 2004. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature 427: 848-853.
129. Stremlau M, Perron M, Lee M, Li Y, Song B, Javanbakht H, Diaz-Griffero F, Anderson DJ, Sundquist WI, Sodroski J. 2006. Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor. Proc Natl Acad Sci 103: 5514-5519.
130. Swan CH, Bühler B, Steinberger P, Tschan MP, Barbas CF III., Torbett BE. 2006. T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery. Gene Ther 13: 1480-1492.
131. Symensma TL, Giver L, Zapp M, Takle GB, Ellington AD. 1996. RNA aptamers selected to bind human immunodeficiency virus type 1 Rev in vitro are Rev responsive in vivo. J Virol 70: 179-187.
132. Tebas P, Stein D, Zifchak L, Seda A, Binder G, Aberra F, Collman R, McGarrity G, Levine B, June C, et al. 2010. Prolonged control of viremia after transfer of autologous CD4 T cells genetically modified with a lentiviral vector expressing long antisense to HIV env (VRX496). In 17th Conference of Retroviruses and Opportunistic Infections. San Francisco.
133. Tomonari A, Takahashi S, Shimohakamada Y, Ooi J, Takasugi K, Ohno N, Konuma T, Uchimaru K, Tojo A, Odawara T, et al. 2005. Unrelated cord blood transplantation for a human immunodeficiency virus-1-seropositive patient with acute lymphoblastic leukemia. Bone Marrow Transpl 36: 261-262.
134. Trobridge GD, Wu RA, Beard BC, Chiu SY, Muñoz NM, von Laer D, Rossi JJ, KiemHP. 2009. Protection of stem cell-derived lymphocytes in a primate AIDS gene therapy model after in vivo selection. PLoS One 4: e7693. doi: 10. 1371/journal. pone. 0007693.
135. + T cells survives cytotoxic chemotherapy. Immunity 31: 834-844.
136. Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. 2010. Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11: 636-646.
137. Valdez H, Connick E, Smith KY, Lederman MM, Bosch RJ, Kim RS, St Clair M, Kuritzkes DR, Kessler H, Fox L, AIDS Clinical Trials Group Protocol 375 Team, et al. 2002. Limited immune restoration after 3 years' suppression of HIV-1 replication in patients with moderately advanced disease. AIDS 16: 1859-1866.
138. van Lunzen J, Glaunsinger T, Stahmer I, von Baehr V, Baum C, Schilz A, Kuehlcke K, Naundorf S, Martinius H, Hermann F, et al. 2007. Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug-resistant virus. Mol Ther 15: 1024-1033.
139. von Laer D, Hasselmann S, Hasselmann K. 2006. Impact of gene-modified T cells on HIV infection dynamics. J Theor Biol 238: 60-77.
140. Walker RE, Bechtel CM, Natarajan V, Baseler M, Hege KM, Metcalf JA, Stevens R, Hazen A, Blaese RM, Chen CC, et al. 2000. Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood 96: 467-474.
141. + T cells. Mol Ther 17: 844-850.
142. + T cells with CXCR4-specific zinc-finger nucleases. PLoS Pathog 7: e1002020. doi: 10. 1371/journal. ppat. 1002020.
143. Woffendin C, Ranga U, Yang Z, Xu L, Nabel GJ. 1996. Expression of a protective gene prolongs survival of T cells in human immunodeficiency virus-infected patients. Proc Natl Acad Sci 93: 2889-2894.
144. Wolf T, Rickerts V, Staszewski S, Kriener S, Wassmann B, Bug G, Bickel M, GuteP, Brodt HR, Martin H. 2007. First case of successful allogeneic stem cell transplantation in an HIV-patient who acquired severe aplastic anemia. Haematologica 92: e56-e58.
145. Wong-Staal F, Poeschla EM, Looney DJ. 1998. A controlled, phase 1 clinical trial to evaluate the safety and effects in HIV-1 infected humans of autologous lymphocytes transduced with a ribozyme that cleaves HIV-1 RNA. Hum Gene Ther 9: 2407-2425.
146. + cell responses following allogeneic hematopoietic cell transplantation. Blood 112: 3484-3487.
147. Xia C, Luo D, Yu X, Jiang S, Liu S. 2011. HIV-associated dementia in the era of highly active antiretroviral therapy (HAART). Microbes Infect 13: 419-425.
148. Yang AG, Bai X, Huang XF, Yao C, Chen S. 1997. Phenotypic knockout of HIV type 1 chemokine coreceptor CCR-5 by intrakines as potential therapeutic approach for HIV-1 infection. Proc Natl Acad Sci 94: 11567.
149. Yap MW, Nisole S, Stoye JP. 2005. A single amino acid change in the SPRY domain of human Trim5 αleads to HIV-1 restriction. Curr Biol 15: 73-78.
150. +memory stem cells in graft-versus-host disease. Nat Med 11: 1299-1305.
151. Zhang J, Wu YO, Xiao L, Li K, Chen LL, Sirois P. 2007. Therapeutic potential of RNA interference against cellular targets of HIV infection. Mol Biotechnol 37: 225-236.
152. + hematopoietic stem cells: An anti-human immunodeficiency virus strategy. J Virol Methods 161: 30-37.
153. Zimmerman PA, Buckler-White A, Alkhatib G, Spalding T, Kubofcik J, Combadiere C, Weissman D, Cohen O, Rubbert A, Lam G, et al. 1997. Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: Studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk. Mol Med 3: 23-36.