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Articles

siRNA: novel therapeutics from functional genomics

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Pages 1-30 | Received 23 Sep 2013, Accepted 05 Jan 2014, Published online: 14 Jul 2014

References

  • Allerson, C. R., Sioufi, N., Jarres, R., Prakash, T., Naik, N., Berdeja, A., … Bhat, B. (2005). Fully 2‘-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA. Journal of Medicinal Chemistry, 48, 901–904.10.1021/jm049167j
  • Audouy, S. A., de Leij, L., Hoekstra, D., & Molema, G. (2002). In vivo characteristics of cationic liposomes as delivery vectors for gene therapy. Pharmaceutical Research, 19, 1599–1605.10.1023/A:1020989709019
  • Aza-Blanc, P., Cooper, C., Wagner, K., Batalov, S., Deveraux, Q., & Cooke, M. (2003). Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening. Molecular Cell, 12, 627–637.10.1016/S1097-2765(03)00348-4
  • Behlke, M. A. (2006). Progress towards in vivo use of siRNAs. Molecular Therapy, 13, 644–670.10.1016/j.ymthe.2006.01.001
  • Behlke, M. A. (2008). Chemical modification of siRNAs for in vivo use. Oligonucleotides, 18, 305–319.
  • Bernstein, E., Caudy, A., Hammond, S., & Hannon, G. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature, 409, 363–366.10.1038/35053110
  • Bitko, V., Musiyenko, A., Shulyayeva, O., & Barik, S. (2005). Inhibition of respiratory viruses by nasally administered siRNA. Nature Medicine, 11, 50–55.10.1038/nm1164
  • Boden, D., Pusch, O., Lee, F., Tucker, L., & Ramratnam, B. (2003). Human immunodeficiency virus type 1 escape from RNA interference. Journal of Virology, 77, 11531–11535.10.1128/JVI.77.21.11531-11535.2003
  • Braasch, D. A., Paroo, Z., Constantinescu, A., Ren, G., Oz, O., Mason, R., & Corey, D. (2004). Biodistribution of phosphodiester and phosphorothioate siRNA. Bioorganic & Medicinal Chemistry Letters, 14, 1139–1143.10.1016/j.bmcl.2003.12.074
  • Bramsen, J. B., & Kjems, J. (2011). Chemical modification of small interfering RNA. Methods Mol. Biol., 721, 77–103.
  • Burnett, J. C., & Rossi, J. (2012). RNA-based therapeutics: Current progress and future prospects. Chemistry & Biology, 19, 60–71.10.1016/j.chembiol.2011.12.008
  • Burnett, J. C., Rossiand, J. J., & Tiemann, K. (2011). Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnology Journal, 6, 1130–1146.10.1002/biot.201100054
  • Castanotto, D., & Rossi, J. (2009). The promises and pitfalls of RNA-interference-based therapeutics. Nature, 457, 426–433.10.1038/nature07758
  • Celotto, A. M., & Graveley, B. (2002). Exon-specific RNAi: A tool for dissecting the functional relevance of alternative splicing. RNA, 8, 718–724.10.1017/S1355838202021064
  • Chang, E., Zhu, M., & Drezek, R. (2007). Novel siRNA-based molecular beacons for dual imaging and therapy. Biotechnology Journal, 2, 1–5.
  • Chien, P. Y., Wang, J., Carbonaro, D., Lei, S., Miller, B., Sheikh, S., … Ahmad, I. (2005). Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo. Cancer Gene Therapy, 12, 321–328.10.1038/sj.cgt.7700793
  • Chollet, P., Favrot, M., Hurbin, A., & Coll, J. (2002). Side-effects of a systemic injection of linear polyethylenimine-DNA complexes. The Journal of Gene Medicine, 4, 84–91.10.1002/(ISSN)1521-2254
  • Choung, S., Kim, Y., Kim, S., Park, H., & Choi, Y. (2006). Chemical modification of siRNAs to improve serum stability without loss of efficacy. Biochemical and Biophysical Research Communications, 342, 919–927.10.1016/j.bbrc.2006.02.049
  • Coburn, G., & Cullen, B. (2003). siRNAs: A new wave of RNA-based therapeutics. Journal of Antimicrobial Chemotherapy, 51, 753–756.10.1093/jac/dkg166
  • Couzin, J. (2002). Breakthrough of the year: Small RNAs make big splash. Science, 298, 2296–2297.10.1126/science.298.5602.2296
  • Das, A. T., Brummelkamp, T., Westerhout, E., Vink, M., Madiredjo, M., Bernards, R., & Berkhout, B. (2004). Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition. Journal of Virology, 78, 2601–2605.10.1128/JVI.78.5.2601-2605.2004
  • DasGupta, R., & Perrimon, N. (2004). Using RNAi to catch Drosophila genes in a web of interactions: Insights into cancer research. Oncogene, 23, 8359–8365.10.1038/sj.onc.1208028
  • Dass, C. R. (2002). Cytotoxicity issues pertinent to lipoplex-mediated gene therapy in vivo. Journal of Pharmacy and Pharmacology, 54, 593–601.10.1211/0022357021778817
  • Davidson, B. L., & McCray, P. (2011). Current prospects for RNA interference-based therapies. Nature Reviews Genetics, 12, 329–340.10.1038/nrg2968
  • de Fougerolles, A., Manoharan, M., Meyers, R., & Vornlocher, H. (2005). RNA interference in vivo: toward synthetic small inhibitory RNA-based therapeutics. Methods Enzymology, 392, 278–296.10.1016/S0076-6879(04)92016-2
  • de Fougerolles, A., Vornlocher, H., Maraganore, J., & Lieberman, J. (2007). Interfering with disease: A progress report on siRNA-based therapeutics. Nature Reviews Drug Discovery, 6, 443–453.10.1038/nrd2310
  • Dorsett, Y., & Tuschl, T. (2004). siRNAs: Applications in functional genomics and potential as therapeutics. Nature Reviews Drug Discovery, 3, 318–329.10.1038/nrd1345
  • Dykxhoorn, D. M., & Lieberman, J. (2006). Knocking down disease with siRNAs. Cell, 126, 231–235.10.1016/j.cell.2006.07.007
  • Eckstein, F. (2002). Developments in RNA chemistry, a personal view. Biochimie, 84, 841–848.10.1016/S0300-9084(02)01459-1
  • Elbashir, S. M., Lendeckel, W., & Tuschl, T. (2001). RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes & Development, 15, 188–200.10.1101/gad.862301
  • Elbashir, S. M., Martinez, J., Patkaniowska, A., Lendeckel, W., & Tuschl, T. (2001). Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. The EMBO Journal, 20, 6877–6888.10.1093/emboj/20.23.6877
  • Faustino, N., & Cooper, T. (2003). Pre-mRNA splicing and human disease. Genes & Development, 17, 419–437.10.1101/gad.1048803
  • Fire, A., Xu, S., Montgomery, M., Kostas, S., Driver, S., & Mello, C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391, 806–811.10.1038/35888
  • Gaglione, M., & Messere, A. (2010). Recent progress in chemically modified siRNAs. Mini Reviews in Medical Chemistry, 10, 578–595.
  • Ge, Q., Filip, L., Bai, A., Nguyen, T., Eisen, H., & Chen, J. (2004). Inhibition of influenza virus production in virus-infected mice by RNA interference. Proceedings of the National Academy of Sciences, 101, 8676–8681.10.1073/pnas.0402486101
  • Grimm, D., Streetz, K., Jopling, C., Storm, T., Pandey, K., Davis, C., Marion, P., Salazar, F., & Kay, M. (2006). Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature, 441, 537–541.10.1038/nature04791
  • Hacein-Bey-Abina, S., von Kalle, C., Schmidt, M., Le Deist, F., Wulffraat, N., McIntyre, E., … Fischer, A. (2003). A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. New England Journal of Medicine, 348, 255–256.10.1056/NEJM200301163480314
  • Haussecker, D. (2012). The business of RNAi therapeutics. Molecular Therapeutics Nuclei Acids, 2, 1–12.
  • He, L., & Hannon, G. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nature Reviews Genetics, 5, 522–531.10.1038/nrg1379
  • Holen, T., Amarzguioui, M., Babaie, E., & Prydz, H. (2003). Similar behaviour of single-strand and double-strand siRNAs suggests they act through a common RNAi pathway. Nucleic Acids Research, 31, 2401–2407.10.1093/nar/gkg338
  • Hornung, V., Guenthner-Biller, M., Bourquin, C., Ablasser, A., Schlee, M., Uematsu, S., … Hartmann, G. (2005). Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nature Medicine, 11, 263–270.10.1038/nm1191
  • Huesken, D., Lange, J., Mickanin, C., Weiler, J., Asselbergs, F., Warner, J., … Hall, J. (2005). Design of a genome-wide siRNA library using an artificial neural network. Nature Biotechnology, 23, 995–1001.10.1038/nbt1118
  • Hu-Lieskovan, S., Heidel, J., Bartlett, D., Davis, M., & Triche, T. (2005). Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing’;s sarcoma. Cancer Research, 65, 8984–8992.10.1158/0008-5472.CAN-05-0565
  • Judge, A. D., Sood, V., Shaw, J., Fang, D., McClintock, K., & Maclachlan, I. (2005). Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nature Biotechnology, 23, 457–462.10.1038/nbt1081
  • Kariko, K., Bhuyan, P., Capodici, J., & Weissman, D. (2004). Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through toll-like receptor 3. The Journal of Immunology, 172, 6545–6549.10.4049/jimmunol.172.11.6545
  • Kenski, D. M., Butora, G., Willingham, A. T., Cooper, A. J., Fu, W., Qi, N., … Flanagan, W. M. (2012). siRNA-optimized modifications for enhanced in vivo activity. Molecular Therapy – Nucleic Acids, 1, e5, doi:10.1038/mtna.2011.410.1038/mtna.2011.4
  • Ketting, R. F., Fischer, S., Bernstein, E., Sijen, T., Hannon, G., & Plasterk, R. (2001). Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes & Development, 15, 2654–2659.10.1101/gad.927801
  • Khvorova, A., Reynolds, A., & Jayasena, S. (2003). Functional siRNAs and miRNAs exhibit strand bias. Cell, 115, 209–216.10.1016/S0092-8674(03)00801-8
  • Kim, D. H., Behlke, M., Rose, S., Chang, M., Choi, S., & Rossi, J. (2005). Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nature Biotechnology, 23, 222–226.10.1038/nbt1051
  • Kim, D. H., & Rossi, J. (2007). Strategies for silencing human disease using RNA interference. Nature Reviews Genetics, 8, 173–184.10.1038/nrg2006
  • Layzer, J. M., McCaffrey, A., Tanner, A., Huang, Z., Kay, M., & Sullenger, B. (2004). In vivo activity of nuclease-resistant siRNAs. RNA, 10, 766–771.10.1261/rna.5239604
  • Li, L., Lin, X., Staver, M., Shoemaker, A., Semizarov, D., Fesik, S., & Shen, Y. (2005). Evaluating hypoxia-inducible factor-1  as a cancer therapeutic target via inducible RNA interference in vivo. Cancer Research, 65, 7249–7258.10.1158/0008-5472.CAN-04-4426
  • Lin, X., Ruan, X., Anderson, M., McDowell, J., Kroeger, P., Fesik, S., & Shen, Y. (2005). siRNA-mediated off-target gene silencing triggered by a 7 nt complementation. Nucleic Acids Research, 33, 4527–4535.10.1093/nar/gki762
  • Liu, J., Carmell, M., Rivas, F., Marsden, C., Thomson, J., Song, J., … Hannon, G. (2004). Argonaute2 is the catalytic engine of mammalian RNAi. Science, 305, 1437–1441.10.1126/science.1102513
  • Liu, Q., Rand, T., Kalidas, S., Du, F., Kim, H., Smith, D., & Wang, X. (2003). R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science, 301, 1921–1925.10.1126/science.1088710
  • Lu, P. Y., Xie, F., & Woodle, M. (2003). siRNA-mediated antitumorgenesis for drug target validation and therapeutics. Current Opinion in Molecular Therapeutics, 5, 225–234.
  • Ma, Z., Li, J., He, F., Wilson, A., Pitt, B., & Li, S. (2005). Cationic lipids enhance siRNA-mediated interferon response in mice. Biochemical and Biophysical Research Communications, 330, 755–759.10.1016/j.bbrc.2005.03.041
  • Manoharan, M. (1999). 2′-Carbohydrate modifications in antisense oligonucleotide therapy: importance of conformation, configuration and conjugation. Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 1489, 117–130.10.1016/S0167-4781(99)00138-4
  • Manoharan, M. (2002). Oligonucleotide conjugates as potential antisense drugs with improved uptake, biodistribution, targeted delivery, and mechanism of action. Antisense and Nucleic Acid Drug Development, 12, 103–128.10.1089/108729002760070849
  • Marques, J. T., & Williams, B. (2005). Activation of the mammalian immune system by siRNAs. Nature Biotechnology, 23, 1399–1405.10.1038/nbt1161
  • Martinez, J., Patkaniowska, A., Urlaub, H., Luhrmann, R., & Tuschl, T. (2002). Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell, 110, 563–574.10.1016/S0092-8674(02)00908-X
  • Matranga, C., Tomari, Y., Shin, C., Bartel, D., & Zamore, P. (2005). Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell, 123, 607–620.10.1016/j.cell.2005.08.044
  • McCaffrey, A. P., Meuse, L., Pham, T., Conklin, D., Hannon, G., & Kay, M. (2002). Gene expression: RNA interference in adult mice. Nature, 418, 38–39.10.1038/418038a
  • McManus, M. T., Haines, B., Dillon, C., Whitehurst, C., van Parijs, L., Chen, J., & Sharp, P. A. (2002). Small interfering RNA-mediated gene silencing in T lymphocytes. The Journal of Immunology, 169, 5754–5760.10.4049/jimmunol.169.10.5754
  • Meister, G., & Tuschl, T. (2004). Mechanisms of gene silencing by double-stranded RNA. Nature, 431, 343–349.10.1038/nature02873
  • Morrissey, D. V., Lockridge, J., Shaw, L., Blanchard, K., Jensen, K., Breen, W., … Polisky, B. (2005). Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nature Biotechnology, 23, 1002–1007.10.1038/nbt1122
  • Nagy, P., Arndt-Jovin, D., & Jovin, T. (2003). Small interfering RNAs suppress the expression of endogenous and GFP-fused epidermal growth factor receptor (erbB1) and induce apoptosis in erbB1-overexpressing cells. Experimental Cell Research, 285, 39–49.10.1016/S0014-4827(02)00050-2
  • Naito, Y., Yoshimura, J., Morishita, S., & Ui-Tei, K. (2009). siDirect 2.0: updated software for designing functional siRNA with reduced seed-dependent off-target effect. BMC Bioinformatics, 10, 392–399.10.1186/1471-2105-10-392
  • Nattanan, T., & Thienprasert, P. (2012). Overview of RNA interference therapeutics. Songklanakarin Journal of Science and Technology, 34, 293–301.
  • Ntambi, J. M., Miyazaki, M., Stoehr, J., Lan, H., Kendziorski, C., Yandell, B., … Attie, A. (2002). Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proceedings of the National Academy of Sciences, 99, 11482–11486.10.1073/pnas.132384699
  • Opalinska, J. B., & Gewirtz, A. (2002). Nucleic-acid therapeutics: Basic principles and recent applications. Nature Reviews Drug Discovery, 1, 503–514.10.1038/nrd837
  • Pei, Y., & Tuschl, T. (2006). On the art of identifying effective and specific siRNAs. Nature Methods, 3, 670–676.10.1038/nmeth911
  • Poulin, G., Nandakumar, R., & Ahringer, J. (2004). Genome-wide RNAi screens in Caenorhabditis elegans: Impact on cancer research. Oncogene, 23, 8340–8345.10.1038/sj.onc.1208010
  • Raoul, C., Abbas-Terki, T., Bensadoun, J., Guillot, S., Haase, G., Szulc, J., … Aebischer, P. (2005). Lentiviral-mediated silencing of SOD1 through RNA interference retards disease onset and progression in a mouse model of ALS. Nature Medicine, 11, 423–428.10.1038/nm1207
  • Rettig, G. R., & Behlke, M. A. (2012). Progress toward in vivo use of siRNAs-II. Molecular Therapy, 20, 483–512.10.1038/mt.2011.263
  • Reynolds, A., Leake, D., Boese, Q., Scaringe, S., Marshall, W., & Khvorova, A. (2004). Rational siRNA design for RNA interference. Nature Biotechnology, 22, 326–330.10.1038/nbt936
  • Reynolds, A., Anderson, E., Vermeulen, A., Fedorov, Y., Robinson, K., Leake, D., … Khvorova, A. (2006). Induction of the interferon response by siRNA is cell type- and duplex length-dependent. RNA, 12, 988–993.10.1261/rna.2340906
  • Ryther, R. C., Flynt, A., Harris, B., Phillips, J., III, & Patton, J. (2004). GH1 splicing is regulated by multiple enhancers whose mutation produces a dominant-negative GH isoform that can be degraded by allele-specific small interfering RNA (siRNA). Journal of Endocrinology, 145, 2988–2996.10.1210/en.2003-1724
  • Ryther, R. C., Flynt, A., Phillips, J., III, & Patton, J. (2005). siRNA therapeutics: Big potential from small RNAs. Gene Therapy, 12, 5–11.10.1038/sj.gt.3302356
  • Scacheri, P. C., Rozenblatt-Rosen, O., Caplen, N., Wolfsberg, T., Umayam, L., Lee, J., … Collins, F. (2004). Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells. Proceedings of the National Academy of Sciences, 101, 1892–1897.10.1073/pnas.0308698100
  • Schwarz, D. S., Hutvágner, G., Du, T., Xu, Z., Aronin, N., & Zamore, P. (2003). Asymmetry in the assembly of the RNAi enzyme complex. Cell, 115, 199–208.10.1016/S0092-8674(03)00759-1
  • Semizarov, D., Frost, L., Sarthy, A., Kroeger, P., Halbert, D., & Fesik, S. (2003). Specificity of short interfering RNA determined through gene expression signatures. Proceedings of the National Academy of Sciences, 100, 6347–6352.10.1073/pnas.1131959100
  • Shirane, D., Sugao, K., Namiki, S., Tanabe, M., Iino, M., & Hirose, K. (2004). Enzymatic production of RNAi libraries from cDNAs. Nature Genetics, 36, 190–196.10.1038/ng1290
  • Simberg, D., Weisman, S., Talmon, Y., & Barenholz, Y. (2004). DOTAP (and other cationic lipids): chemistry, biophysics, and transfection. Critical Reviews in Therapeutic Drug Carrier Systems, 21, 257–317.10.1615/CritRevTherDrugCarrierSyst.v21.i4
  • Sorensen, D. R., Leirdal, M., & Sioud, M. (2003). Gene silencing by systemic delivery of synthetic siRNAs in adult mice. Journal of Molecular Biology, 327, 761–766.10.1016/S0022-2836(03)00181-5
  • Soutschek, J., Akinc, A., Bramlage, B., Charisse, K., Constien, R., Donoghue, M., … Vornlocher, H. (2004). Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature, 432, 173–178.10.1038/nature03121
  • Thakker, D. R., Natt, F., Hüsken, D., Maier, R., Müller, M., van der Putten, H., Hoyer, D., & Cryan, J. (2004). Neurochemical and behavioral consequences of widespread gene knockdown in the adult mouse brain by using nonviral RNA interference. Proceedings of the National Academy of Sciences, 101, 17270–17275.10.1073/pnas.0406214101
  • Tiemann, K., & Rossi, J. J. (2009). RNAi-based therapeutics-current status, challenges and prospects. EMBO Molecular Medicine, 1, 142–151.10.1002/emmm.200900023
  • Tousignant, J. D., Gates, A., Ingram, L., Johnson, C., Nietupski, J., Cheng, S., … Scheule, R. (2000). Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid: plasmid DNA complexes in mice. Hum. Gene Ther., 11, 2493–2513.
  • Urban-Klein, B., Werth, S., Abuharbeid, S., Czubayko, F., & Aigner, A. (2005). RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene Therapy, 12, 461–466.10.1038/sj.gt.3302425
  • Vaishnaw, A. K., Gollob, J., Gamba-Vitalo, C., Hutabarat, R., Sah, D., Meyers, R., … Maraganore, J. (2010). A status report on RNAi therapeutics. Silence, 1, 14.10.1186/1758-907X-1-14
  • Victor, M. M., Xia, H., Marrs, G., Gouvion, C., Lee, G., Davidson, B., & Paulson, H. (2003). Allele-specific silencing of dominant disease genes. Proceedings of National Academy of Science USA, 100, 7195–7200.
  • Wang, J., Lu, Z., & Guillaume, W. (2010). Delivery of siRNA therapeutics: Barriers and carriers. The AAPS Journal, 12, 492–503.10.1208/s12248-010-9210-4
  • Weinstein, S., & Peer, D. (2010). RNAi nanomedicines: Challanges and opportunities within the immune system. Nanotechnology, 21, 1–13.
  • Yi, R., Qin, Y., Macara, I., & Cullen, B. (2003). Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes & Development, 17, 3011–3016.10.1101/gad.1158803
  • Zhang, W., Yang, H., Kong, X., Mohapatra, S., San Juan-Vergara, H., Hellermann, G., … Mohapatra, S. (2005). Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene. Nature Medicine, 11, 56–62.10.1038/nm1174
  • Zhao, L. N., Li, T., Pan, Y., Ning, H., Liu, Z., & Fan, D. (2005). Application of siRNA Library in High-Throughput Genetic Screens of Mammalian Cells. Journal of Cancer Molecules, 1, 19–24.
  • Zhou, J., Shum, K., Burnett, J. C., & Rossi, J. (2013). Nanoparticle-based delivery of RNAi therapeutics: Progress and challenges. Pharmaceuticals, 6, 85–107.10.3390/ph6010085

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