Toward a durable anti-HIV gene therapy based on RNA interference

Annals of the New York Academy of Sciences

Volumn 1175, Issue , 2009, Pages 3-14

  Berkhout, Ben ^a  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

Combination therapy; Gene therapy; HIS mouse; HIV 1; Lentiviral vector; RNAi; Viral escape; Virus evolution

Indexed keywords

ANTIRETROVIRUS AGENT; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4; CYCLIN T1; EMERIN; FURIN; GAG PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LENS EPITHELIUM DERIVED GROWTH FACTOR; LENTIVIRUS VECTOR; MICRORNA; NEF PROTEIN; P21 ACTIVATED KINASE 1; POL PROTEIN; REV PROTEIN; SHORT HAIRPIN RNA; SMALL INTERFERING RNA; TRANSACTIVATOR PROTEIN; VIRUS VECTOR;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL ACTIVITY; CLINICAL TRIAL; CONFERENCE PAPER; GENE SEQUENCE; GENE SILENCING; GENE THERAPY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MUTATION RATE; NONHUMAN; RNA INTERFERENCE; STEM CELL GENE THERAPY; VIRUS INFECTION; VIRUS REPLICATION;

CAENORHABDITIS ELEGANS; HUMAN IMMUNODEFICIENCY VIRUS 1; MAMMALIA;

EID: 70349444994     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2009.04972.x     Document Type: Conference Paper

References (133)

1. Fire, A., S. Xu, M.K. Montgomery, S.A. Kostas, et al. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391 : 806 811. (Pubitemid 28099681)
2. He, L. G.J. Hannon. 2004. MicroRNAs: small RNAs with a big role in gene regulation. Nat. Rev. Genet. 5 : 522 531.
3. Elbashir, S.M., J. Harborth, W. Lendeckel, et al. 2001. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411 : 494 498.
4. Brummelkamp, T.R., R. Bernards R. Agami. 2002. A system for stable expression of short interfering RNAs in mammalian cells. Science 296 : 550 553.
5. Hammond, S.M., E. Bernstein, D. Beach G.J. Hannon. 2000. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404 : 293 296.
6. Kim, D. J. Rossi. 2008. RNAi mechanisms and applications. Biotechn. 44 : 613 616.
7. Dykxhoorn, D.M., D. Chowdhury J. Lieberman. 2008. RNA interference and cancer: endogenous pathways and therapeutic approaches. Adv. Exp. Med. Biol. 615 : 299 329.
8. Jaskiewicz, L. W. Filipowicz. 2008. Role of Dicer in posttranscriptional RNA silencing. Curr. Top. Microbiol. Immunol. 320 : 77 97.
9. Paddison, P.J. 2008. RNA interference in mammalian cell systems. Curr. Top. Microbiol. Immunol. 320 : 1 19.
10. Bitko, V., A. Musiyenko, O. Shulyayeva S. Barik. 2005. Inhibition of respiratory viruses by nasally administered siRNA. Nat. Med. 11 : 50 55.
11. Haasnoot, P.C.J., D. Cupac B. Berkhout. 2003. Inhibition of virus replication by RNA interference. J. Biomed. Sc. 10 : 607 616.
12. Ge, Q., L. Filip, A. Bai, et al. 2004. Inhibition of influenza virus production in virus-infected mice by RNA interference. Proc. Natl. Acad. Sci. USA 101 : 8676 8681.
13. Li, B.J. et al. 2005. Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque. Nat. Med. 11 : 944 951.
14. Kleinman, M.E. et al. 2008. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452 : 591 597.
15. Robbins, M., A. Judge, E. Ambegia, et al. 2008. Misinterpreting the therapeutic effects of siRNA caused by immune stimulation. Hum.Gene Ther. 19 : 991 999.
16. Kumar, P. et al. 2008. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 134 : 577 586.
17. Ter Brake, O., K. 't Hooft, Y.P. Liu, et al. 2008. Lentiviral vector design for multiple shRNA expression and durable HIV-1 Inhibition. Mol. Ther. 16 : 557 564.
18. Haasnoot, J., E.M. Westerhout B. Berkhout. 2007. RNA interference against viruses: strike and counterstrike. Nat. Biotechnol. 25 : 1435 1443.
19. Grimm, D. M.A. Kay. 2007. Combinatorial RNAi: a winning strategy for the race against evolving targets? Mol. Ther. 15 : 878 888.
20. Li, H.W. S.W. Ding. 2005. Antiviral silencing in animals. FEBS Lett. 579 : 5965 5973.
21. Leonard, J.N. D.V. Schaffer. 2006. Antiviral RNAi therapy: emerging approaches for hitting a moving target. Gene Ther. 13 : 532 540.
22. Liu, Y.P. B. Berkhout. 2008. Combinatorial RNAi strategies against HIV-1 and other escape-prone viruses. Int. J. BioSci. Technol. 1 : 1 10.
23. Scherer, L., J.J. Rossi M.S. Weinberg. 2007. Progress and prospects: RNA-based therapies for treatment of HIV infection. Gene Ther. 14 : 1057 1064.
24. Stram, Y. L. Kuzntzova. 2006. Inhibition of viruses by RNA interference. Virus Gen. 32 : 299 306.
25. Haasnoot, P.C.J. B. Berkhout. 2006. RNA interference: Its use as antiviral therapy. In Handbook of Experimental Pharmacology, pp. 117 150. Heidelberg.
26. Berkhout, B. 2004. RNA interference as an antiviral approach: targeting HIV-1. Curr. Opin. Mol. Ther. 6 : 141 145.
27. Lee, N.S. J.J. Rossi. 2004. Control of HIV-1 replication by RNA interference. Virus Res. 102 : 53 58.
28. Anderson, J., M.J. Li, B. Palmer, et al. 2007. Safety and efficacy of a lentiviral vector containing three anti-HIV genes-CCR5 ribozyme, tat-rev siRNA, and TAR decoy-in SCID-hu mouse-derived T cells. Mol. Ther. 14 : 1182 1188.
29. Grimm, D. M.A. Kay. 2007. Therapeutic application of RNAi: is mRNA targeting finally ready for prime time? J. Clin. Invest. 117 : 3633 3641.
30. Boden, D., O. Pusch, F. Lee, et al. 2003. Human immunodeficiency virus type 1 escape from RNA interference. J. Virol. 77 : 11531 11535.
31. Boden, D., O. Pusch, F. Lee, et al. 2004. Efficient gene transfer of HIV-1-specific short hairpin RNA into human lymphocytic cells using recombinant adeno-associated virus vectors. Mol. Ther. 9 : 396 402.
32. Boden, D., O. Pusch, R. Silbermann, et al. 2004. Enhanced gene silencing of HIV-1 specific siRNA using microRNA designed hairpins. Nucleic Acids Res. 32 : 1154 1158.
33. Das, A.T., T.R. Brummelkamp, E.M. Westerhout, et al. 2004. Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition. J. Virol. 78 : 2601 2605.
34. Westerhout, E.M., M. Ooms, M. Vink, et al. 2005. HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome. Nucleic Acids Res. 33 : 796 804.
35. Westerhout, E.M., M. Vink, P.C. Haasnoot, et al. 2006. A conditionally replicating HIV-based vector that stably expresses an antiviral shRNA against HIV-1 replication. Mol. Ther. 14 : 268 275.
36. Ter Brake, O., P. Konstantinova, M. Ceylan B. Berkhout. 2006. Silencing of HIV-1 with RNA interference: a multiple shRNA approach. Mol. Ther. 14 : 883 892.
37. von Eije, K.J., O. ter Brake B. Berkhout. 2008. Human immunodeficiency virus type 1 escape is restricted when conserved genome sequences are targeted by RNA interference. J. Virol. 82 : 2895 28903.
38. Martinez, M.A., B. Clotet J.A. Este. 2002. RNA interference of HIV replication. Trends Immunol. 23 : 559 561.
39. Martinez, M.A., A. Gutierrez, M. Armand-Ugon, et al. 2002. Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication. AIDS 16 : 2385 2390.
40. Sabariegos, R., M. Gimenez-Barcons, N. Tapia, et al. 2006. Sequence homology required by human immunodeficiency virus type 1 to escape from short interfering RNAs. J. Virol. 80 : 571 577.
41. Anderson, J., A. Banerjea R. Akkina. 2003. Bispecific short hairpin siRNA constructs targeted to CD4, CXCR4, and CCR5 confer HIV-1 resistance. Oligonucleotides 13 : 303 312.
42. Barichievy, S., S. Saayman, K.J. von Eije, et al. 2007. The inhibitory efficacy of RNA POL III-expressed long hairpin RNAs targeted to untranslated regions of the HIV-1 5′ long terminal repeat. Oligonucleotides 17 : 419 431.
43. Boden, D., O. Pusch, F. Lee, et al. 2003. Promoter choice affects the potency of HIV-1 specific RNA interference. Nucleic Acids Res. 31 : 5033 5038.
44. Capodici, J., K. Kariko D. Weissman. 2002. Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J. Immunol. 169 : 5196 5201.
45. Chiu, Y.L., H. Cao, J.M. Jacque, et al. 2004. Inhibition of human immunodeficiency virus type 1 replication by RNA interference directed against human transcription elongation factor P-TEFb (CDK9/CyclinT1). J. Virol. 78 : 2517 2529.
46. Huff, B. 2004. News from the bench. Assay for less-fit phenotype? GMHC. Treat. Issues 18 : 14.
47. Konstantinova, P., O. ter Brake, J. Haasnoot, et al. 2007. Trans-inhibition of HIV-1 by a long hairpin RNA expressed within the viral genome. Retrovirology 4 : 15.
48. Lawrence, D. 2002. RNAi could hold promise in the treatment of HIV. Lancet 359 : 2007.
49. Li, Z., Y. Xiong, Y. Peng, et al. 2005. Specific inhibition of HIV-1 replication by short hairpin RNAs targeting human cyclin T1 without inducing apoptosis. FEBS Lett. 579 : 3100 3106.
50. Liu, Y.P., J. Haasnoot B. Berkhout. 2007. Design of extended short hairpin RNAs for HIV-1 inhibition. Nucleic Acids Res. 35 : 5683 5693.
51. Liu, Y.P., J. Haasnoot, O. ter Brake, et al. 2008. Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA polycistron. Nucleic Acids Res. 36 : 2811 2824.
52. Nishitsuji, H., T. Ikeda, H. Miyoshi, et al. 2004. Expression of small hairpin RNA by lentivirus-based vector confers efficient and stable gene-suppression of HIV-1 on human cells including primary non-dividing cells. Microbes. Infect. 6 : 76 85.
53. Omoto, S., M. Ito, Y. Tsutsumi, et al. 2004. HIV-1 nef suppression by virally encoded microRNA. Retrovirology 1 : 44 55.
54. Ping, Y.H., C.Y. Chu, H. Cao, et al. 2004. Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5. Retrovirology 1 : 46.
55. Rossi, J.J. 2006. RNAi as a treatment for HIV-1 infection. Biotechn. Suppl : 25 29.
56. Saayman, S., S. Barichievy, A. Capovilla, et al. 2008. The efficacy of generating three independent anti-HIV-1 siRNAs from a single U6 RNA Pol III-expressed long hairpin RNA. PLoS ONE 3 : e2602.
57. Son, J., P.D. Uchil, Y.B. Kim, et al. 2008. Effective suppression of HIV-1 by artificial bispecific miRNA targeting conserved sequences with tolerance for wobble base-pairing. Biochem. Biophys. Res. Commun. 374 : 214 218.
58. Ter Brake, O. B. Berkhout. 2005. A novel approach for inhibition of HIV-1 by RNA interference: counteracting viral escape with a second generation of siRNAs. J. RNAi Gene Silencing 1 : 56 65.
59. Yamamoto, T., S. Omoto, M. Mizuguchi, et al. 2002. Double-stranded nef RNA interferes with human immunodeficiency virus type 1 replication. Microbiol. Immunol. 46 : 809 817.
60. Yamamoto, T., H. Miyoshi, N. Yamamoto, et al. 2006. Lentivirus vectors expressing short hairpin RNAs against the U3-overlapping region of HIV nef inhibit HIV replication and infectivity in primary macrophages. Blood 108 : 3305 3312.
61. Zhou, N., J. Fang, M. Mukhtar, et al. 2004. Inhibition of HIV-1 fusion with small interfering RNAs targeting the chemokine coreceptor CXCR4. Gene Ther. 11 : 1703 1712.
62. Ter Brake, O., J. Haasnoot, J. Kurreck B. Berkhout. 2008. ESF-EMBO symposium: antiviral applications of RNA interference. Retrovirology 5 : 81.
63. Naito, Y., K. Nohtomi, T. Onogi, et al. 2007. Optimal design and validation of antiviral siRNA for targeting HIV-1. Retrovirology 4 : 80.
64. Coburn, G.A. B.R. Cullen. 2002. Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference. J. Virol. 76 : 9225 9231.
65. Jacque, J.M., K. Triques M. Stevenson. 2002. Modulation of HIV-1 replication by RNA interference. Nature 418 : 435 438.
66. Joshi, P.J., T.W. North V.R. Prasad. 2005. Aptamers directed to HIV-1 reverse transcriptase display greater efficacy over small hairpin RNAs targeted to viral RNA in blocking HIV-1 replication. Mol. Ther. 11 : 677 686.
67. Nishitsuji, H., M. Kohara, M. Kannagi T. Masuda. 2006. Effective suppression of human immunodeficiency virus type 1 through a combination of short- or long-hairpin RNAs targeting essential sequences for retroviral integration. J. Virol. 80 : 7658 7666.
68. Surabhi, R.M. R.B. Gaynor. 2002. RNA interference directed against viral and cellular targets inhibits human immunodeficiency virus type 1 replication. J. Virol. 76 : 12963 12973.
69. Hu, W.Y., C.P. Myers, J.M. Kilzer, et al. 2002. Inhibition of retroviral pathogenesis by RNA interference. Curr. Biol. 12 : 1301 1311.
70. Westerhout, E.M., O. ter Brake B. Berkhout. 2006. The virion-associated incoming HIV-1 RNA genome is not targeted by RNA interference. Retrovirology 3 : 57 65.
71. Gao, Y., M.A. Lobritz, J. Roth, et al. 2008. Targets of small interfering RNA restriction during human immunodeficiency virus type 1 replication. J. Virol. 82 : 2938 2951.
72. Morris, K.V. 2008. RNA-mediated transcriptional gene silencing in human cells. Curr. Top. Microbiol. Immunol. 320 : 211 224.
73. Kawasaki, H. K. Taira. 2004. Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature 431 : 211 217.
74. Suzuki, K., T. Shijuuku, T. Fukamachi, et al. 2005. Prolonged transcriptional silencing and CpG methylation induced by dsRNAs targeted to the HIV-1 promoter region. J. RNAi Gene Silencing 1 : 66 78.
75. Andersson, M.G., P.C.J. Haasnoot, N. Xu, et al. 2005. Suppression of RNA interference by adenovirus virus-associated RNA. J. Virol. 79 : 9556 9565.
76. de Vries, W. B. Berkhout. 2008. RNAi suppressors encoded by pathogenic human viruses. Int. J. Biochem. Cell Biol. 40 : 2007 2012.
77. Haasnoot, J., W. de Vries, E.J. Geutjes, et al. 2007. The Ebola virus VP35 protein is a suppressor of RNA silencing. PLoS Pathog. 3 : e86.
78. Bennasser, Y., S.Y. Le, M. Benkirane K.T. Jeang. 2005. Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing. Immunity 22 : 607 619.
79. Schnettler, E., W. de Vries, H. Hemmes, et al. 2009. The NS3 protein of rice hoja blanca virus complements the RNAi suppressor function of HIV-1 Tat. EMBO Rep. 10 : 258 263.
80. Henry, S.D., P. Van Der Wegen, H.J. Metselaar, et al. 2006. Simultaneous targeting of HCV replication and viral binding with a single lentiviral vector containing multiple RNA interference expression cassettes. Mol. Ther. 14 : 485 493.
81. von Eije, K.J., O. ter Brake B. Berkhout. 2009. Stringent testing identifies highly potent and escape-proof anti-HIV shRNAs. J. Gene Med. 11 : 459 467.
82. Ter Brake, O., K.J. von Eije B. Berkhout. 2008. Probing the sequence space available for HIV-1 evolution. AIDS 22 : 1875 1877.
83. Lee, S.K., D.M. Dykxhoorn, P. Kumar, et al. 2005. Lentiviral delivery of short hairpin RNAs protects CD4 T cells from multiple clades and primary isolates of HIV. Blood 106 : 818 826.
84. Unwalla, H.J., H.T. Li, I. Bahner, et al. 2006. Novel Pol II fusion promoter directs human immunodeficiency virus type 1-inducible coexpression of a short hairpin RNA and protein. J. Virol. 80 : 1863 1873.
85. Westerhout, E.M. B. Berkhout. 2007. A systematic analysis of the effect of target RNA structure on RNA interference. Nucleic Acids Res. 35 : 4322 4330.
86. Leonard, J.N., P.S. Shah, J.C. Burnett D.V. Schaffer. 2008. HIV evades RNA interference directed at TAR by an indirect compensatory mechanism. Cell Host. Microbe 4 : 484 494.
87. Berkhout, B. 2009. A new Houdini act: multiple routes for HIV-1 escape from RNA interference mediated inhibition. Future Microbiology 4 : 151 154.
88. Berkhout, B., K. Verhoef, J.L.B. van Wamel B. Back. 1999. Genetic instability of live-attenuated HIV-1 vaccine strains. J. Virol. 73 : 1138 1145.
89. Hannon, G.J. J.J. Rossi. 2004. Unlocking the potential of the human genome with RNA interference. Nature 431 : 371 378.
90. Shankar, P., N. Manjunath J. Lieberman. 2005. The prospect of silencing disease using RNA interference. JAMA 293 : 1367 1373.
91. Stevenson, M. 2003. Dissecting HIV-1 through RNA interference. Nat. Rev. Immunol. 3 : 851 858.
92. Keulen, W., N.K.T. Back, A. van Wijk, et al. 1997. Initial appearance of the 184Ile variant in lamivudine-treated patients is caused by the mutational bias of the human immunodeficiency virus type 1 Reverse Transcriptase. J. Virol. 71 : 3346 3350.
93. Keulen, W., C. Boucher B. Berkhout. 1996. Nucleotide substitution patterns can predict the requirements for drug-resistance of HIV-1 proteins. Antiviral Res. 31 : 45 57.
94. Mansky, L.M. 1996. The mutation rate of human immunodeficiency virus type 1 is influenced by the vpr gene. Virol 222 : 391 400.
95. Anderson, J. R. Akkina. 2005. HIV-1 resistance conferred by siRNA cosuppression of CXCR4 and CCR5 coreceptors by a bispecific lentiviral vector. AIDS Res. Ther. 2 : 1.
96. Llano, M., D.T. Saenz, A. Meehan, et al. 2006. An essential role for LEDGF/p75 in HIV integration. Science 314 : 461 464.
97. Maertens, G., P. Cherepanov, W. Pluymers, et al. 2003. LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J. Biol. Chem. 278 : 33528 33539. (Pubitemid 37055807)
98. Jacque, J.M. M. Stevenson. 2006. The inner-nuclear-envelope protein emerin regulates HIV-1 infectivity. Nature 441 : 641 645.
99. Nguyen, D.G., K.C. Wolff, H. Yin, et al. 2006. "UnPAKing" human immunodeficiency virus (HIV) replication: using small interfering RNA screening to identify novel cofactors and elucidate the role of group I PAKs in HIV Infection. J. Virol. 80 : 130 137.
100. Jopling, C.L., M. Yi, A.M. Lancaster, et al. 2005. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 309 : 1577 1581.
101. Jopling, C.L., S. Schütz P. Sarnow. 2008. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host. Microbe 4 : 77 85.
102. Gottwein, E., N. Mukherjee, C. Sachse, et al. 2007. A viral microRNA functions as an orthologue of cellular miR-155. Nature 450 : 1096 1099.
103. Gottwein, E. B.R. Cullen. 2008. Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host. Microbe 3 : 375 387.
104. Umbach, J.L., M.F. Kramer, I. Jurak, et al. 2008. MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature 454 : 780 783.
105. Berkhout, B. K.T. Jeang. 2007. RISCy business: microRNAs, pathogenesis, and viruses. J. Biol. Chem. 282 : 26641 26645.
106. Berkhout, B. 2008. A balancing act: viruses and miRNAs. J. Formosan Med. Assoc. 107 : 1 3.
107. Henke, J.I., D. Goergen, J. Zheng, et al. 2008. microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J. 27 : 3300 3310.
108. Houzet, L., M.L. Yeung, V. de Lame, et al. 2008. MicroRNA profile changes in human immunodeficiency virus type 1 (HIV-1) seropositive individuals. Retrovirology 5 : 118.
109. Liu, R., W.A. Paxton, S. Choe, et al. 1996. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86 : 367 377.
110. de Roda Husman, A.M., H. Blaak, M. Brouwer H. Schuitemaker. 1999. CC chemokine receptor 5 cell-surface expression in relation to CC chemokine receptor 5 genotype and the clinical course of HIV-1 infection. J. Immunol. 163 : 4597 4603.
111. An, D.S., R.E. Donahue, M. Kamata, et al. 2007. Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates. Proc. Natl. Acad. Sci. USA 104 : 13110 13115.
112. Aagaard, L. J.J. Rossi. 2007. RNAi therapeutics: principles, prospects and challenges. Adv. Drug Deliv. Rev. 59 : 75 86.
113. Ter Brake, O. B. Berkhout. 2008. Development of an RNAi-based gene therapy against HIV-1. In Therapeutic Oligonucleotides. J. Kurreck, Ed. : 296 311. RSC Publishing, Cambridge.
114. Banerjea, A., M.J. Li, G. Bauer, et al. 2003. Inhibition of HIV-1 by lentiviral vector-transduced siRNAs in T lymphocytes differentiated in SCID-hu mice and CD34+ progenitor cell-derived macrophages. Mol. Ther. 8 : 62 71.
115. Chang, L.J., X. Liu J. He. 2005. Lentiviral siRNAs targeting multiple highly conserved RNA sequences of human immunodeficiency virus type 1. Gene Ther. 12 : 1133 1144.
116. Ter Brake, O. B. Berkhout. 2007. Lentiviral vectors that carry anti-HIV shRNAs: problems and solutions. J. Gene. Med. 9 : 743 750.
117. An, W. A. Telesnitsky. 2001. Frequency of direct repeat deletion in a human immunodeficiency virus type 1 vector during reverse transcription in human cells. Virol 286 : 475 482.
118. Weinberg, M.S., A. Ely, S. Barichievy, et al. 2007. Specific inhibition of HBV replication in vitro and in vivo with expressed long hairpin RNA. Mol. Ther. 15 : 534 541.
119. Grimm, D., K.L. Streetz, C.L. Jopling, et al. 2006. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441 : 537 541.
120. Bridge, A.J., S. Pebernard, A. Ducraux, et al. 2003. Induction of an interferon response by RNAi vectors in mammalian cells. Nat. Genet. 34 : 263 264.
121. Hornung, V., M. Guenthner-Biller, C. Bourguin, et al. 2005. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med. 11 : 263 270.
122. Pebernard, S. R.D. Iggo. 2004. Determinants of interferon-stimulated gene induction by RNAi vectors. Differentiation 72 : 103 111.
123. Robbins, M.A. J.J. Rossi. 2005. Sensing the danger in RNA. Nat. Med. 11 : 250 251.
124. Sioud, M. 2005. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J. Mol. Biol. 348 : 1079 1090.
125. Birmingham, A., E.M. Anderson, A. Reynolds, et al. 2006. 3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods 3 : 199 204.
126. Jackson, A.L., J. Burchard, J. Schelter, et al. 2006. Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. RNA 12 : 1179 1187.
127. Lin, X., X. Ruan, M.G. Anderson, et al. 2005. siRNA-mediated off-target gene silencing triggered by a 7 nt complementation. Nucleic Acids Res. 33 : 4527 4535.
128. Legrand, N., K. Weijer H. Spits. 2006. Experimental models to study development and function of the human immune system in vivo. J. Immunol. 176 : 2053 2058.
129. Ter Brake, O., N. Legrand, K.J. von Eije, et al. 2009. Evaluation of safety and efficacy of RNAi against HIV-1 in the human immune system (Rag-2(-/-)(c)(-/-)) mouse model. Gene Ther. 16 : 148 153.
130. Baenziger, S., R. Tussiwand, E. Schlaepfer, et al. 2006. Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-gamma c-/- mice. Proc. Natl. Acad. Sci. USA 103 : 15951 15956.
131. Berges, B.K., W.H. Wheat, B.E. Palmer, et al. 2006. HIV-1 infection and CD4 T cell depletion in the humanized Rag2-/-gamma c-/- (RAG-hu) mouse model. Retrovirology 3 : 76.
132. Zhang, L., G.I. Kovalev L. Su. 2007. HIV-1 infection and pathogenesis in a novel humanized mouse model. Blood 109 : 2978 2981.
133. Hütter, G., D. Nowak, M. Mossner, et al. 2009. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N. Engl. J. Med. 360 : 692 698.