文献・巻末表・謝辞

• Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J.
  Basic local alignment search tool.
  J. Mol. Biol. 215, 403-410 (1990).
• Amarzguioui, M. & Prydz, H.
  An algorithm for selection of functional siRNA sequences.
  Biochem. Biophys. Res. Commun. 316, 1050-1058 (2004).
• Banerjea, A., Li, M.-J., Bauer, G., Remling, L., Lee, N.-S., Rossi, J. & Akkina, R.
  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 (2003).
• Benson, D.A., Karsch-Mizrachi, I., Lipman, D.J., Ostell, J. & Wheeler, D.L.
  GenBank.
  Nucleic Acids Res. 35, D21-D25 (2007).
• Bernstein, E., Caudy, A.A., Hammond, S.M. & Hannon, G.J.
  Role for a bidentate ribonuclease in the initiation step of RNA interference.
  Nature 409, 363-366 (2001).
• Birmingham, A., Anderson, E.M., Reynolds, A., Ilsley-Tyree, D., Leake, D., Fedorov, Y., Baskerville, S., Maksimova, E., Robinson, K., Karpilow, J., Marshall, W.S. & Khvorova, A.
  3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets.
  Nat. Methods 3, 199-204 (2006).
• Boden, D., Pusch, O., Lee, F., Tucker, L. & Ramratnam, B.
  Human immunodeficiency virus type 1 escape from RNA interference.
  J. Virol. 77, 11531-11535 (2003a).
• Boden, D., Pusch, O., Lee, F., Tucker, L., Shank, P.R. & Ramratnam, B.
  Promoter choice affects the potency of HIV-1 specific RNA interference.
  Nucleic Acids Res. 31, 5033-5038 (2003b).
• Boden, D., Pusch, O., Lee, F., Tucker, L. & Ramratnam, B.
  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 (2004a).
• Boden, D., Pusch, O., Silbermann, R., Lee, F., Tucker, L. & Ramratnam, B.
  Enhanced gene silencing of HIV-1 specific siRNA using microRNA designed hairpins.
  Nucleic Acids Res. 32, 1154-1158 (2004b).
• Capodici, J., Karikó, K. & Weissman, D.
  Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference.
  J. Immunol. 169, 5196-5201 (2002).
• Chang, L.-J., Liu, X. & He, J.
  Lentiviral siRNAs targeting multiple highly conserved RNA sequences of human immunodeficiency virus type 1.
  Gene Ther. 12, 1133-1144 (2005).
• Chendrimada, T.P., Gregory, R.I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K. & Shiekhattar, R.
  TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing.
  Nature 436, 740-744 (2005).
• Coburn, G.A. & Cullen, B.R.
  Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference.
  J. Virol. 76, 9225-9231 (2002).
• Das, A.T., Brummelkamp, T.R., Westerhout, E.M., Vink, M., Madiredjo, M., Bernards, R. & Berkhout, B.
  Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition.
  J. Virol. 78, 2601-2605 (2004).
• Dave, R.S. & Pomerantz, R.J.
  Antiviral effects of human immunodeficiency virus type 1-specific small interfering RNAs against targets conserved in select neurotropic viral strains.
  J. Virol. 78, 13687-13696 (2004).
• Doi, N., Zenno, S., Ueda, R., Ohki-Hamazaki, H., Ui-Tei, K. & Saigo, K.
  Short-interfering-RNA-mediated gene silencing in mammalian cells requires Dicer and eIF2C translation initiation factors.
  Curr. Biol. 13, 41-46 (2003).
• Du, Q., Thonberg, H., Wang, J., Wahlestedt, C. & Liang, Z.
  A systematic analysis of the silencing effects of an active siRNA at all single-nucleotide mismatched target sites.
  Nucleic Acids Res. 33, 1671-1677 (2005).
• Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. & Tuschl, T.
  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells.
  Nature 411, 494-498 (2001a).
• Elbashir, S.M., Lendeckel, W. & Tuschl, T.
  RNA interference is mediated by 21- and 22-nucleotide RNAs.
  Genes Dev. 15, 188-200 (2001b).
• Elbashir, S.M., Martinez, J., Patkaniowska, A., Lendeckel, W. & Tuschl, T.
  Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate.
  EMBO J. 20, 6877-6888 (2001c).
• Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E. & Mello, C.C.
  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.
  Nature 391, 806-811 (1998).
• Grant, C.E., Vasa, M.Z. & Deeley, R.G.
  cIRF-3, a new member of the interferon regulatory factor (IRF) family that is rapidly and transiently induced by dsRNA.
  Nucleic Acids Res. 23, 2137-2146 (1995).
• Hammond, S.M., Boettcher, S., Caudy, A.A., Kobayashi, R. & Hannon, G.J.
  Argonaute2, a link between genetic and biochemical analyses of RNAi.
  Science 293, 1146-1150 (2001).
• Han, W., Wind-Rotolo, M., Kirkman, R.L. & Morrow, C.D.
  Inhibition of human immunodeficiency virus type 1 replication by siRNA targeted to the highly conserved primer binding site.
  Virology 330, 221-232 (2004).
• Holen, T., Amarzguioui, M., Wiiger, M.T., Babaie, E. & Prydz, H.
  Positional effects of short interfering RNAs targeting the human coagulation trigger Tissue Factor.
  Nucleic Acids Res. 30, 1757-1766 (2002).
• Hu, W.-Y., Myers, C.P., Kilzer, J.M., Pfaff, S.L. & Bushman, F.D.
  Inhibition of retroviral pathogenesis by RNA interference.
  Curr. Biol. 12, 1301-1311 (2002).
• Huelsmann, P.M., Rauch, P., Allers, K., John, M.J. & Metzner, K.J.
  Inhibition of drug-resistant HIV-1 by RNA interference.
  Antiviral Res. 69, 1-8 (2006).
• Huthoff, H. & Berkhout, B.
  Two alternating structures of the HIV-1 leader RNA.
  RNA 7, 143-157 (2001).
• Jackson, A.L. & Linsley, P.S.
  Noise amidst the silence: off-target effects of siRNAs?
  Trends Genet. 20, 521-524 (2004).
• Jacque, J.-M., Triques, K. & Stevenson, M.
  Modulation of HIV-1 replication by RNA interference.
  Nature 418, 435-438 (2002).
• Joshi, P.J., North, T.W. & Prasad, V.R.
  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 (2005).
• Kaufman, R.J.
  Double-stranded RNA-activated protein kinase mediates virus-induced apoptosis: a new role for an old actor.
  Proc. Natl. Acad. Sci. USA 96, 11693-11695 (1999).
• Kennerdell, J.R. & Carthew, R.W.
  Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway.
  Cell 95, 1017-1026 (1998).
• Ketting, R.F., Fischer, S.E.J., Bernstein, E., Sijen, T., Hannon, G.J. & Plasterk, R.H.A.
  Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans.
  Genes Dev. 15, 2654-2659 (2001).
• Khvorova, A., Reynolds, A. & Jayasena, S.D.
  Functional siRNAs and miRNAs exhibit strand bias.
  Cell 115, 209-216 (2003).
• Kittler, R., Heninger, A.-K., Franke, K., Habermann, B. & Buchholz, F.
  Production of endoribonuclease-prepared short interfering RNAs for gene silencing in mammalian cells.
  Nat. Methods 2, 779-784 (2005).
• Kuiken, C., Yusim, K., Boykin, L. & Richardson, R.
  The Los Alamos hepatitis C sequence database.
  Bioinformatics 21, 379-384 (2005).
• Lee, M.-T.M., Coburn, G.A., McClure, M.O. & Cullen, B.R.
  Inhibition of human immunodeficiency virus type 1 replication in primary macrophages by using Tat- or CCR5-specific small interfering RNAs expressed from a lentivirus vector.
  J. Virol. 77, 11964-11972 (2003).
• Lee, N.-S., Dohjima, T., Bauer, G., Li, H., Li, M.-J., Ehsani, A., Salvaterra, P. & Rossi, J.
  Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells.
  Nat. Biotechnol. 20, 500-505 (2002).
• Lee, S.-K., Dykxhoorn, D.M., Kumar, P., Ranjbar, S., Song, E., Maliszewski, L.E., François-Bongarçon, V., Goldfeld, A., Swamy, N.M., Lieberman, J. & Shankar, P.
  Lentiviral delivery of short hairpin RNAs protects CD4 T cells from multiple clades and primary isolates of HIV.
  Blood 106, 818-826 (2005).
• Lee, Y., Hur, I., Park, S.-Y., Kim, Y.-K., Suh, M.R. & Kim, V.N.
  The role of PACT in the RNA silencing pathway.
  EMBO J. 25, 522-532 (2006).
• Leonard, J.N. & Schaffer, D.V.
  Antiviral RNAi therapy: emerging approaches for hitting a moving target.
  Gene Ther. 13, 532-540 (2006).
• Li, M.-J., Bauer, G., Michienzi, A., Yee, J.-K., Lee, N.-S., Kim, J., Li, S., Castanotto, D., Zaia, J. & Rossi, J.J.
  Inhibition of HIV-1 infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs.
  Mol. Ther. 8, 196-206 (2003).
• Li, M.-J., Kim, J., Li, S., Zaia, J., Yee, J.-K., Anderson, J., Akkina, R. & Rossi, J.J.
  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 (2005).
• Lim, L.P., Lau, N.C., Garrett-Engele, P., Grimson, A., Schelter, J.M., Castle, J., Bartel, D.P., Linsley, P.S. & Johnson, J.M.
  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.
  Nature 433, 769-773 (2005).
• Lin, S.-L. & Ying, S.-Y.
  Combinational therapy for potential HIV-1 eradication and vaccination.
  Int. J. Oncol. 24, 81-88 (2004).
• Lin, X., Ruan, X., Anderson, M.G., McDowell, J.A., Kroeger, P.E., Fesik, S.W. & Shen, Y.
  siRNA-mediated off-target gene silencing triggered by a 7 nt complementation.
  Nucleic Acids Res. 33, 4527-4535 (2005).
• Ma, J.-B., Yuan, Y.-R., Meister, G., Pei, Y., Tuschl, T. & Patel, D.J.
  Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein.
  Nature 434, 666-670 (2005).
• Martinez, J., Patkaniowska, A., Urlaub, H., Lührmann, R. & Tuschl, T.
  Single-stranded antisense siRNAs guide target RNA cleavage in RNAi.
  Cell 110, 563-574 (2002).
• Naito, Y., Yamada, T., Ui-Tei, K., Morishita, S. & Saigo, K.
  siDirect: highly effective, target-specific siRNA design software for mammalian RNA interference.
  Nucleic Acids Res. 32, W124-W129 (2004).
• Naito, Y., Yamada, T., Matsumiya, T., Ui-Tei, K., Saigo, K. & Morishita, S.
  dsCheck: highly sensitive off-target search software for double-stranded RNA-mediated RNA interference.
  Nucleic Acids Res. 33, W589-W591 (2005).
• Naito, Y., Ui-Tei, K., Nishikawa, T., Takebe, Y. & Saigo, K.
  siVirus: web-based antiviral siRNA design software for highly divergent viral sequences.
  Nucleic Acids Res. 34, W448-W450 (2006).
• Nishitsuji, H., Ikeda, T., Miyoshi, H., Ohashi, T., Kannagi, M. & Masuda, T.
  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 (2004).
• Nishitsuji, H., Kohara, M., Kannagi, M. & Masuda, T.
  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 (2006).
• Novina, C.D., Murray, M.F., Dykxhoorn, D.M., Beresford, P.J., Riess, J., Lee, S.-K., Collman, R.G., Lieberman, J., Shankar, P. & Sharp, P.A.
  siRNA-directed inhibition of HIV-1 infection.
  Nat. Med. 8, 681-686 (2002).
• Park, W.-S., Hayafune, M., Miyano-Kurosaki, N. & Takaku, H.
  Specific HIV-1 env gene silencing by small interfering RNAs in human peripheral blood mononuclear cells.
  Gene Ther. 10, 2046-2050 (2003).
• Parker, J.S., Roe, S.M. & Barford, D.
  Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex.
  Nature 434, 663-666 (2005).
• Paul, C.P., Good, P.D., Li, S.X.L., Kleihauer, A., Rossi, J.J. & Engelke, D.R.
  Localized expression of small RNA inhibitors in human cells.
  Mol. Ther. 7, 237-247 (2003).
• Pruitt, K.D., Tatusova, T. & Maglott, D.R.
  NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins.
  Nucleic Acids Res. 35, D61-D65 (2007).
• Pusch, O., Boden, D., Silbermann, R., Lee, F., Tucker, L. & Ramratnam, B.
  Nucleotide sequence homology requirements of HIV-1-specific short hairpin RNA.
  Nucleic Acids Res. 31, 6444-6449 (2003).
• Reynolds, A., Leake, D., Boese, Q., Scaringe, S., Marshall, W.S. & Khvorova, A.
  Rational siRNA design for RNA interference.
  Nat. Biotechnol. 22, 326-330 (2004).
• Sabariegos, R., Giménez-Barcons, M., Tàpia, N., Clotet, B. & Martínez, M.A.
  Sequence homology required by human immunodeficiency virus type 1 to escape from short interfering RNAs.
  J. Virol. 80, 571-577 (2006).
• Scherer, L.J., Yildiz, Y., Kim, J., Cagnon, L., Heale, B. & Rossi, J.J.
  Rapid assessment of anti-HIV siRNA efficacy using PCR-derived Pol III shRNA cassettes.
  Mol. Ther. 10, 597-603 (2004).
• Schwarz, D.S., Hutvágner, G., Du, T., Xu, Z., Aronin, N. & Zamore, P.D.
  Asymmetry in the assembly of the RNAi enzyme complex.
  Cell 115, 199-208 (2003).
• Song, E., Lee, S.-K., Dykxhoorn, D.M., Novina, C., Zhang, D., Crawford, K., Cerny, J., Sharp, P.A., Lieberman, J., Manjunath, N. & Shankar, P.
  Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophages.
  J. Virol. 77, 7174-7181 (2003).
• Song, J.-J., Smith, S.K., Hannon, G.J. & Joshua-Tor, L.
  Crystal structure of Argonaute and its implications for RISC slicer activity.
  Science 305, 1434-1437 (2004).
• Surabhi, R.M. & Gaynor, R.B.
  RNA interference directed against viral and cellular targets inhibits human immunodeficiency virus type 1 replication.
  J. Virol. 76, 12963-12973 (2002).
• Suzuki, K., Shijuuku, T., Fukamachi, T., Zaunders, J., Guillemin, G., Cooper, D. & Kelleher, A.
  Prolonged transcriptional silencing and CpG methylation induced by siRNAs targeted to the HIV-1 promoter region.
  J. RNAi Gene Silencing 1, 66-78 (2005).
• Takebe, Y., Motomura, K., Tatsumi, M., Lwin, H.H., Zaw, M. & Kusagawa, S.
  High prevalence of diverse forms of HIV-1 intersubtype recombinants in Central Myanmar: geographical hot spot of extensive recombination.
  AIDS 17, 2077-2087 (2003).
• ter Brake, O., Konstantinova, P., Ceylan, M. & Berkhout, B.
  Silencing of HIV-1 with RNA interference: a multiple shRNA approach.
  Mol. Ther. 14, 883-892 (2006).
• Ui-Tei, K., Zenno, S., Miyata, Y. & Saigo, K.
  Sensitive assay of RNA interference in Drosophila and Chinese hamster cultured cells using firefly luciferase gene as target.
  FEBS Lett. 479, 79-82 (2000).
• Ui-Tei, K., Naito, Y., Takahashi, F., Haraguchi, T., Ohki-Hamazaki, H., Juni, A., Ueda, R. & Saigo, K.
  Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference.
  Nucleic Acids Res. 32, 936-948 (2004).
• Ui-Tei, K., Naito, Y. & Saigo, K.
  Guidelines for the selection of effective short-interfering RNA sequences for functional genomics.
  Methods Mol. Biol. 361, 201-216 (2006).
• Unwalla, H.J., Li, M.-J., Kim, J.D., Li, H.T., Ehsani, A., Alluin, J. & Rossi, J.J.
  Negative feedback inhibition of HIV-1 by TAT-inducible expression of siRNA.
  Nat. Biotechnol. 22, 1573-1578 (2004).
• Unwalla, H.J., Li, H.-T., Bahner, I., Li, M.-J., Kohn, D. & Rossi, J.J.
  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 (2006).
• Wargelius, A., Ellingsen, S. & Fjose, A.
  Double-stranded RNA induces specific developmental defects in zebrafish embryos.
  Biochem. Biophys. Res. Commun. 263, 156-161 (1999).
• Westerhout, E.M., Ooms, M., Vink, M., Das, A.T. & Berkhout, B.
  HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome.
  Nucleic Acids Res. 33, 796-804 (2005).
• Westerhout, E.M., ter Brake, O. & Berkhout, B.
  The virion-associated incoming HIV-1 RNA genome is not targeted by RNA interference.
  Retrovirology 3, 57 (2006a).
• Westerhout, E.M., Vink, M., Haasnoot, P.C.J., Das, A.T. & Berkhout, B.
  A conditionally replicating HIV-based vector that stably expresses an antiviral shRNA against HIV-1 replication.
  Mol. Ther. 14, 268-275 (2006b).
• Willey, R.L., Smith, D.H., Lasky, L.A., Theodore, T.S., Earl, P.L., Moss, B., Capon, D.J. & Martin, M.A.
  In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity.
  J. Virol. 62, 139-147 (1988).
• Yamada, T. & Morishita, S.
  Accelerated off-target search algorithm for siRNA.
  Bioinformatics 21, 1316-1324 (2005).
• Yamamoto, T., Miyoshi, H., Yamamoto, N., Yamamoto, N., Inoue, J. & Tsunetsugu-Yokota, Y.
  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 (2006).
• Yoshinari, K., Miyagishi, M. & Taira, K.
  Effects on RNAi of the tight structure, sequence and position of the targeted region.
  Nucleic Acids Res. 32, 691-699 (2004).
• Yuan, Y.-R., Pei, Y., Ma, J.-B., Kuryavyi, V., Zhadina, M., Meister, G., Chen, H.-Y., Dauter, Z., Tuschl, T. & Patel, D.J.
  Crystal structure of A. aeolicus argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage.
  Mol. Cell 19, 405-419 (2005).

本研究の機会を恵与され，終始多大なる御指導，御鞭撻を賜りました東京大学教授 西郷 薫博士に謹んで感謝の意を表しますとともに，厚く御礼申し上げます．

本研究全般にわたり直接御指導を賜り，また，本論文の校閲を戴きました東京大学助教授 程 久美子博士ならびに国立感染症研究所室長 武部 豊博士に謹んで謝意を表しますとともに，共同研究を通じて終始御懇篤なる御指導，御討論を賜りました東京大学教授 森下 真一博士ならびに東京大学特任助手 山田 智之氏に深謝いたします．

また，数々の御助言，御討論を戴きました国立遺伝学研究所教授 上田 龍博士，前橋工科大学助教授 善野 修平博士，東京大学助手 高橋 史峰博士に厚く御礼申し上げます．

さらに，実験に御協力，御援助を戴きました江田 理愛氏，田中 愛氏ならびに西郷研究室，程研究室の皆様に感謝いたします．

[PDF] 配列表