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Engineering Cell Function by RNA Interference

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Cell Line Development

Part of the book series: Cell Engineering ((CEEN,volume 6))

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Abstract

RNA interference (RNAi) is a recently discovered technique for the directed inhibition of gene expression at the level of the mRNA. Its specificity and potency make it a promising method for manipulating cellular phenotypes in eukaryotic cell lines and primary cells. RNAi is already being explored for therapeutic and bioprocessing applications, and it is expected that this will only expand as understanding of the mechanism increases. In this chapter, the mechanism of RNAi is described, followed by a description of some of the technical challenges that remain to realize the full benefits of RNAi. The progress to date on RNAi-based applications will also be detailed.

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References

  • Akinc A, Zumbuehl A, Goldberg M, Leshchiner ES, Busini V, Hossain N, Bacallado SA, Nguyen DN, Fuller J, Alvarez R et al (2008) A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat Biotech 26:561–569

    Article  CAS  Google Scholar 

  • Allen RS, Millgate AG, Chitty JA, Thisleton J, Miller JA, Fist AJ, Gerlach WL, Larkin PJ (2004) RNAi-mediated replacement of morphine with the nonnarcotic alkaloid reticuline in opium poppy. Nat Biotechnol 22:1559–1566

    Article  PubMed  CAS  Google Scholar 

  • Allen RS, Miller JA, Chitty JA, Fist AJ, Gerlach WL, Larkin PJ (2008) Metabolic engineering of morphinan alkaloids by over-expression and RNAi suppression of salutaridinol 7-O-acetyltransferase in opium poppy. Plant Biotechnol J 6:22–30

    PubMed  CAS  Google Scholar 

  • Alper H, Fischer C, Nevoigt E, Stephanopoulos G (2005) Tuning genetic control through promoter engineering. Proc Natl Acad Sci U S A 102:12678–12683

    Article  PubMed  CAS  Google Scholar 

  • Amarzguioui M, Holen T, Babaie E, Prydz H (2003) Tolerance for mutations and chemical modifications in a siRNA. Nucleic Acids Res 31:589–595

    Article  PubMed  CAS  Google Scholar 

  • Ameres SL, Martinez J, Schroeder R (2007) Molecular basis for target RNA recognition and cleavage by human RISC. Cell 130:101–112

    Article  PubMed  CAS  Google Scholar 

  • Arntzen C, Plotkin S, Dodet B (2005) Plant-derived vaccines and antibodies: potential and limitations. Vaccine 23:1753–1756

    Article  PubMed  CAS  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  • Bartlett DW, Davis ME (2007) Physicochemical and biological characterization of targeted, nucleic acid-containing nanoparticles. Bioconjug Chem 18:456–468

    Article  PubMed  CAS  Google Scholar 

  • Bartlett DW, Su H, Hildebrandt IJ, Weber WA, Davis ME (2007) Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc Natl Acad Sci U S A 104:15549–15554

    Article  PubMed  CAS  Google Scholar 

  • Bernstein E, Caudy AA, Hammond SM, Hannon GJ (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363–366

    Article  PubMed  CAS  Google Scholar 

  • Bohula EA, Salisbury AJ, Sohail M, Playford MP, Riedemann J, Southern EM, Macaulay VM (2003) The efficacy of small interfering RNAs targeted to the type 1 insulin-like growth factor receptor (IGF1R) is influenced by secondary structure in the IGF1R transcript. J Biol Chem 278:15991–15997

    Article  PubMed  CAS  Google Scholar 

  • Brown KM, Chu CY, Rana TM (2005) Target accessibility dictates the potency of human RISC. Nat Struct Mol Biol 12:469–470

    Article  PubMed  CAS  Google Scholar 

  • Brus C, Petersen H, Aigner A, Czubayko F, Kissel T (2004) Physicochemical and biological characterization of polyethylenimine-graft-poly(ethylene glycol) block copolymers as a delivery system for oligonucleotides and ribozymes. Bioconjug Chem 15:677–684

    Article  PubMed  CAS  Google Scholar 

  • Carmell MA, Xuan Z, Zhang MQ, Hannon GJ (2002) The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev 16:2733–2742

    Article  PubMed  CAS  Google Scholar 

  • Cheah MT, Wachter A, Sudarsan N, Breaker RR (2007) Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature 447:497–500

    Article  PubMed  CAS  Google Scholar 

  • Chen ZY, He CY, Ehrhardt A, Kay MA (2003) Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo. Mol Ther 8:495–500

    Article  PubMed  CAS  Google Scholar 

  • Chen PY, Weinmann L, Gaidatzis D, Pei Y, Zavolan M, Tuschl T, Meister G (2008) Strand-specific 5′-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity. RNA 14:263–274

    Article  PubMed  CAS  Google Scholar 

  • Chiu Y, Rana TM (2002) RNAi in human cells: basic structural and functional features of small interfering RNA. Mol Cell 10:549–561

    Article  PubMed  CAS  Google Scholar 

  • Clamme JP, Azoulay J, Mely Y (2003) Monitoring of the formation and dissociation of polyethylenimine/DNA complexes by two photon fluorescence correlation spectroscopy. Biophys J 84:1960–1968

    Article  PubMed  CAS  Google Scholar 

  • Corey DR (2007) Chemical modification: the key to clinical application of RNA interference? J Clin Invest 117:3615–3622

    Article  PubMed  CAS  Google Scholar 

  • Cox KM, Sterling JD, Regan JT, Gasdaska JR, Frantz KK, Peele CG, Black A, Passmore D, Moldovan-Loomis C, Srinivasan M et al (2006) Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat Biotechnol 24:1591–1597

    Article  PubMed  CAS  Google Scholar 

  • Crooke ST (2004) Progress in antisense technology. Annu Rev Med 55:61–95

    Article  PubMed  CAS  Google Scholar 

  • Cui Q, Yu Z, Pan Y, Purisima EO, Wang E (2007) MicroRNAs preferentially target the genes with high transcriptional regulation complexity. Biochem Biophys Res Commun 352:733–738

    Article  PubMed  CAS  Google Scholar 

  • Daniell H, Streatfield SJ, Wycoff K (2001) Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci 6:219–226

    Article  PubMed  CAS  Google Scholar 

  • de Fougerolles A, Vornlocher HP, Maraganore J, Lieberman J (2007) Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 6:443–453

    Article  PubMed  CAS  Google Scholar 

  • de Fougerolles AR (2008) Delivery vehicles for small interfering RNA in vivo Hum Gene Ther 19:125–132

    Article  PubMed  CAS  Google Scholar 

  • DeVincenzo J, Cehelsky JE, Alvarez R, Elbashir S, Harborth J, Toudjarska I, Nechev L, Murugaiah V, Van Vliet A, Vaishnaw AK, Meyers R (2008) Evaluation of the safety, tolerability and pharmacokinetics of ALN-RSV01, a novel RNAi antiviral therapeutic directed against respiratory syncytial virus (RSV). Antiviral Res 77:225–231

    Article  PubMed  CAS  Google Scholar 

  • Ding Y, Chan CY, Lawrence CE (2004) Sfold web server for statistical folding and rational design of nucleic acids. Nucleic Acids Res 32:W135–W141

    Article  PubMed  CAS  Google Scholar 

  • Dodo HW, Konan KN, Chen FC, Egnin M, Viquez OM (2008) Alleviating peanut allergy using genetic engineering: the silencing of the immunodominant allergen Ara h 2 leads to its significant reduction and a decrease in peanut allergenicity. Plant Biotechnol J 6:135–145

    Article  PubMed  CAS  Google Scholar 

  • Dong L, Hulsmeyer M, Durkop H, Hansen HP, Schneider-Mergener J, Ziegler A, Uchanska-Ziegler B (2003) Human CD30: structural implications from epitope mapping and modeling studies. J Mol Recognit 16:28–36

    Article  PubMed  CAS  Google Scholar 

  • Doos BR (2002) Population growth and loss of arable land. Global Environ Chang 12:303–311

    Article  Google Scholar 

  • Elbashir SM, Lendeckel W, Tuschl T (2001a) RNA interference is mediated by 21- and 22- nucleotide RNAs. Genes Dev 15:188–200

    Article  PubMed  CAS  Google Scholar 

  • Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T (2001b) Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate Embo J 20:6877–6888

    Article  PubMed  CAS  Google Scholar 

  • Elbashir SM, Harborth J, Weber K, Tuschl T (2002) Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods 26:199–213

    Article  PubMed  CAS  Google Scholar 

  • Elmen J, Thonberg H, Ljungberg K, Frieden M, Westergaard M, Xu Y, Wahren B, Liang Z, Orum H, Koch T, Wahlestedt C (2005) Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Res 33:439–447

    Article  PubMed  CAS  Google Scholar 

  • Far R, Sczakiel G (2003) The activity of siRNA in mammalian cells is related to structural target accessibility: a comparison with antisense oligonucleotides. Nucleic Acids Res 31:4417–4424

    Article  CAS  Google Scholar 

  • Farran I, Sanchez-Serrano JJ, Medina JF, Prieto J, Mingo-Castel AM (2002) Targeted expression of human serum albumin to potato tubers. Transgenic Res 11:337–346

    Article  PubMed  CAS  Google Scholar 

  • Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci U S A 84:7413–7417

    Google Scholar 

  • Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811

    Article  PubMed  CAS  Google Scholar 

  • Floss DM, Falkenburg D, Conrad U (2007) Production of vaccines and therapeutic antibodies for veterinary applications in transgenic plants: an overview. Trangenic Res 16:315–332

    Article  CAS  Google Scholar 

  • Frankard V, Ghislain M, Jacobs M (1992) Two feedback-insensitive enzymes of the aspartate pathway in nicotiana sylvestris. Plant Physiol 99:1285–1293

    Article  PubMed  CAS  Google Scholar 

  • Gallitaliadoros LA, Sedgwick JD, Wood SA, Korner H (1995) Gene knock-out technology – a methodological overview for the interested novice. J Immunol Methods 181:1–15

    Article  CAS  Google Scholar 

  • Ge G, Wong GW, Luo B (2005) Prediction of siRNA knockdown efficiency using artificial neural network models. Biochem Biophys Res Commun 336: 723–728

    Article  PubMed  CAS  Google Scholar 

  • Gomord V, Chamberlain P, Jefferis R, Faye L (2005) Biopharmaceutical production in plants: problems, solutions and opportunities. Trends Biotechnol 23:559–565

    Article  PubMed  CAS  Google Scholar 

  • Gredell JA, Berger AK, Walton SP (2008) Impact of target mRNA structure on siRNA silencing efficiency: a large-scale study. Biotechnol Bioeng 100:744–755

    Article  PubMed  CAS  Google Scholar 

  • Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, Marion P, Salazar F, Kay MA (2006) Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441:537–541

    Article  PubMed  CAS  Google Scholar 

  • Grothe T, Lenz R, Kutchan TM (2001) Molecular characterization of the salutaridinol 7-O-acetyltransferase involved in morphine biosynthesis in opium poppy Papaver somniferum. J Biol Chem 276:30717–30723

    Article  PubMed  CAS  Google Scholar 

  • Haley B, Zamore PD (2004) Kinetic analysis of the RNAi enzyme complex. Nat Struct Mol Biol 11:599–606

    Article  PubMed  CAS  Google Scholar 

  • Hammond SM, Caudy AA, Hannon GJ (2001) Post-transcriptional gene silencing by double-stranded RNA. Nat Rev Genet 2:110–119

    Article  PubMed  CAS  Google Scholar 

  • Hannon GJ (2002) RNA interference. Nature 418:244–251

    Article  PubMed  CAS  Google Scholar 

  • Heale BS, Soifer HS, Bowers C, Rossi JJ (2005) siRNA target site secondary structure predictions using local stable substructures. Nucleic Acids Res 33:e30

    Article  PubMed  CAS  Google Scholar 

  • Hofacker IL (2003) Vienna RNA secondary structure server. Nucleic Acids Res 31:3429–3431

    Article  PubMed  CAS  Google Scholar 

  • Hu-Lieskovan S, Heidel JD, Bartlett DW, Davis ME, Triche TJ (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 Res 65:8984–8992

    Article  PubMed  CAS  Google Scholar 

  • Jackson AL, Linsley PS (2004) Noise amidst the silence: off-target effects of siRNAs? Trends Genet 20:521–524

    Article  PubMed  CAS  Google Scholar 

  • Jagla B, Aulner N, Kelly PD, Song DA, Volchuk A, Zatorski A, Shum D, Mayer T, De Angelis DA, Ouerfelli O et al (2005) Sequence characteristics of functional siRNAs. RNA 11:864–872

    Article  PubMed  CAS  Google Scholar 

  • Kamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, Gotta M, Kanapin A, Le Bot N, Moreno S, Sohrmann M et al (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421:231–237

    Article  PubMed  CAS  Google Scholar 

  • Khvorova A, Reynolds A, Jayasena SD (2003) Functional siRNAs and miRNAs exhibit strand bias. Cell 115:209–216

    Article  PubMed  CAS  Google Scholar 

  • Kim EJ, Kramer SF, Hebert CG, Valdes JJ, Bentley WE (2007) Metabolic engineering of the baculovirus-expression system via inverse “shotgun” genomic analysis and RNA interference (dsRNA) increases product yield and cell longevity. Biotechnol Bioeng 98:645–654

    Article  PubMed  CAS  Google Scholar 

  • Kim YS, Lee YH, Kim HS, Kim MS, Hahn KW, Ko JH, Joung H, Jeon JH (2008) Development of patatin knockdown patato tubers using RNA interference (RNAi) technology, for the production of human-therapeutic glycoproteins. BMC Biotechnol 8:36

    Article  PubMed  CAS  Google Scholar 

  • Kircheis R, Wightman L, Wagner E (2001) Design and gene delivery activity of modified polyethylenimines. Adv Drug Deliv Rev 53:341–358

    Article  PubMed  CAS  Google Scholar 

  • Kleinman ME, Yamada K, Takeda A, Chandrasekaran V, Nozaki M, Baffi JZ, Albuquerque RJC, Yamasaki S, Itaya M, Pan Y et al (2008) Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452:591–597

    Article  PubMed  CAS  Google Scholar 

  • Koppelman SJ, Wensing M, Ertmann M, Knulst AC, Knol EF (2004) Relevance of Ara h1, Ara h2 and Ara h3 in peanut-allergic patients, as determined by immunoglobulin E Western blotting, basophil-histamine release and intracutaneous testing: Ara h2 is the most important peanut allergen. Clin Exp Allegry 34: 583–590

    Article  CAS  Google Scholar 

  • Kumar N, Gammell P, Meleady P, Henry M, Clynes M (2008) Differential protein expression following low temperature culture of suspension CHO-K1 cells. BMC Biotechnol 8:42

    Article  PubMed  CAS  Google Scholar 

  • Kunath K, von Harpe A, Petersen H, Fischer D, Voigt K, Kissel T, Bickel U (2002) The structure of PEG-modified poly(ethylene imines) influences biodistribution and pharmacokinetics of their complexes with NF-kappaB decoy in mice. Pharm Res 19:810–817

    Article  PubMed  CAS  Google Scholar 

  • Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419

    Article  PubMed  CAS  Google Scholar 

  • Liao JC (2004) Custom design of metabolism. Nat Biotechnol 22:823–824

    Article  PubMed  CAS  Google Scholar 

  • Lim SF, Chuan KH, Liu S, Loh SO, Chung BY, Ong CC, Song Z (2006) RNAi suppression of Bax and Bak enhances viability in fed-batch cultures of CHO cells. Metab Eng 8: 509–522

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–1441

    Article  PubMed  CAS  Google Scholar 

  • Lu ZJ, Mathews DH (2007) Efficient siRNA selection using hybridization thermodynamics. Nucleic Acids Res 36: 640–647

    Article  PubMed  CAS  Google Scholar 

  • MacRae IJ, Ma E, Zhou M, Robinson CV, Doudna JA (2008) In vitro reconstitution of the human RISC-loading complex. Proc Natl Acad Sci U S A 105:512–517

    Article  PubMed  CAS  Google Scholar 

  • Mandal M, Breaker RR (2004) Gene regulation by riboswitches. Nat Rev Mol Cell Biol 5:451–463

    Article  PubMed  CAS  Google Scholar 

  • Mao S, Neu M, Germershaus O, Merkel O, Sitterberg J, Bakowsky U, Kissel T (2006) Influence of polyethylene glycol chain length on the physicochemical and biological properties of poly(ethylene imine)-graft-poly(ethylene glycol) block copolymer/SiRNA polyplexes. Bioconjug Chem 17:1209–1218

    Article  PubMed  CAS  Google Scholar 

  • Markham NR, Zuker M (2008) UNAFold: software for nucleic acid folding and hybridization. Methods Mol Biol 453:3–31

    Article  PubMed  CAS  Google Scholar 

  • Matranga C, Tomari Y, Shin C, Bartel DP, Zamore PD (2005) Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123:607–620

    Article  PubMed  CAS  Google Scholar 

  • Maxwell MM, Pasinelli P, Kazantsev AG, Brown RH Jr (2004) RNA interference-mediated silencing of mutant superoxide dismutase rescues cyclosporin A-induced death in cultured neuroblastoma cells. Proc Natl Acad Sci U S A 101:3178–3183

    Article  PubMed  CAS  Google Scholar 

  • McBride JL, Boudreau RL, Harper SQ, Staber PD, Monteys AM, Martins I, Gilmore BL, Burstein H, Peluso RW, Polisky B et al (2008) Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi. Proc Natl Acad Sci U S A 105:5868–5873

    Article  PubMed  CAS  Google Scholar 

  • Neuenschwander U, Suter M, Brunold C (1991) Regulation of sulfate assimilation by light and O-acetyl-l-serine in lemna minor L. Plant Physiol 97:253–258

    Article  PubMed  CAS  Google Scholar 

  • Overhoff M, Alken M, Far RK, Lemaitre M, Lebleu B, Sczakiel G, Robbins I (2005) Local RNA target structure influences siRNA efficacy: a systematic global analysis. J Mol Biol 348:871–881

    Article  PubMed  CAS  Google Scholar 

  • Page JE (2005) Silencing nature’s narcotics: metabolic engineering of the opium poppy. Trends Biotechnol 23:331–333

    Article  PubMed  CAS  Google Scholar 

  • Pardridge WM (2007) shRNA and siRNA delivery to the brain. Adv Drug Deliv Rev 59:141–152

    Article  PubMed  CAS  Google Scholar 

  • Patzel V, Rutz S, Dietrich I, Koberle C, Scheffold A, Kaufmann SH (2005) Design of siRNAs producing unstructured guide-RNAs results in improved RNA interference efficiency. Nat Biotechnol 23:1440–1444

    Article  PubMed  CAS  Google Scholar 

  • Prat S, Frommer WB, Hofgen R, Keil M, Kossmann J, Koster-Topfer M, Liu XJ, Muller B, Pena-Cortes H, Rocha-Sosa M et al (1990) Gene expression during tuber development in potato plants. FEBS Lett 268:334–338

    Article  PubMed  CAS  Google Scholar 

  • Pun SH, Bellocq NC, Liu A, Jensen G, Machemer T, Quijano E, Schluep T, Wen S, Engler H, Heidel J, Davis ME (2004). Cyclodextrin-modified polyethylenimine polymers for gene ­delivery. Bioconjug Chem 15:831–840

    Article  PubMed  CAS  Google Scholar 

  • Rana TM (2007) Illuminating the silence: understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol 8:23–36

    Article  PubMed  CAS  Google Scholar 

  • Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS, Khvorova A (2004) Rational siRNA design for RNA interference. Nat Biotechnol 22:326–330

    Article  PubMed  CAS  Google Scholar 

  • Rozema DB, Ekena K, Lewis DL, Loomis AG, Wolff JA (2003) Endosomolysis by masking of a membrane-active agent (EMMA) for cytoplasmic release of macromolecules. Bioconjug Chem 14:51–57

    Article  PubMed  CAS  Google Scholar 

  • Rozema DB, Lewis DL, Wakefield DH, Wong SC, Klein JJ, Roesch PL, Bertin SL, Reppen TW, Chu Q, Blokhin AV et al (2007) Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes. Proc Natl Acad Sci U S A 104:12982–12987

    Article  PubMed  CAS  Google Scholar 

  • Schubert S, Grunweller A, Erdmann VA, Kurreck J (2005) Local RNA target structure influences siRNA efficacy: systematic analysis of intentionally designed binding regions. J Mol Biol 348:883–893

    Article  PubMed  CAS  Google Scholar 

  • Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, Zamore PD (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199–208

    Article  PubMed  CAS  Google Scholar 

  • Schwarz DS, Ding H, Kennington L, Moore JT, Schelter J, Burchard J, Linsley PS, Aronin N, Xu Z, Zamore PD (2006) Designing siRNA that distinguish between genes that differ by a single nucleotide. PLoS Genet 2:e140

    Article  PubMed  Google Scholar 

  • Shah JK, Garner HR, White MA, Shames DS, Minna JD (2007) sIR: siRNA information resource, a web-based tool for siRNA sequence design and analysis and an open access siRNA database. BMC Bioinformatics 8:178

    Article  PubMed  CAS  Google Scholar 

  • Shao Y, Chan CY, Maliyekkel A, Lawrence CE, Roninson IB, Ding Y (2007) Effect of target secondary structure on RNAi efficiency. RNA 13:1–10

    Article  CAS  Google Scholar 

  • Sicherer SH, Munoz-Furlong A, Burks AW, Sampson HA (1999) Prevalence of peanut and tree nut allergy in the US determined by a random digit dial telephone survey. J Allergy Clin Immunol 103:559–562

    Article  PubMed  CAS  Google Scholar 

  • Singh J, Sharp PJ, Skerritt JH (2001) A new candidate protein for high lysine content in wheat grain. J Sci Food Agr 81:216–226

    Article  CAS  Google Scholar 

  • Sonnichsen B, Koski LB, Walsh A, Marschall P, Neumann B, Brehm M, Alleaume AM, Artelt J, Bettencourt P, Cassin E et al (2005) Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434:462–469

    Article  PubMed  CAS  Google Scholar 

  • Srivastava S, Li Z, Yang X, Yedwabnick M, Shaw S, Chan C (2007) Identification of genes that regulate multiple cellular processes/responses in the context of lipotoxicity to hepatoma cells. BMC Genomics 8:364

    Article  PubMed  Google Scholar 

  • Sunilkumar G, Campbell LM, Puckhaber L, Stipanovic RD, Rathore KS (2006) Engineering cottonseed for use in human nutrition by tissue-specific reduction of toxic gossypol. Proc Natl Acad Sci U S A 103:18054–18059

    Article  PubMed  CAS  Google Scholar 

  • Svoboda P (2007) Off-targeting and other non-specific effects of RNAi experiments in mammalian cells. Curr Opin Mol Ther 9:248–257

    PubMed  CAS  Google Scholar 

  • Swami A, Aggarwal A, Pathak A, Patnaik S, Kumar P, Singh Y, Gupta KC (2007a). Imidazolyl-PEI modified nanoparticles for enhanced gene delivery. Int J Pharm 335:180–192.

    PubMed  CAS  Google Scholar 

  • Swami A, Kurupati RK, Pathak A, Singh Y, Kumar P, Gupta KC (2007) A unique and highly efficient non-viral DNA/siRNA delivery system based on PEI-bisepoxide nanoparticles. Biochem Biophys Res Commun 362:835–841

    Article  PubMed  CAS  Google Scholar 

  • Tafer H, Ameres SL, Obernosterer G, Gebeshuber CA, Schroeder R, Martinez J, Hofacker IL (2008) The impact of target site accessibility on the design of effective siRNAs. Nat Biotechnol 26:578–583

    Article  PubMed  CAS  Google Scholar 

  • Takashima Y, Saito R, Nakajima A, Oda M, Kimura A, Kanazawa T, Okada H (2007) Spray-drying preparation of microparticles containing cationic PLGA nanospheres as gene carriers for avoiding aggregation of nanospheres. Int J Pharm 343:262–269

    Article  PubMed  CAS  Google Scholar 

  • Tang GL, Galili G, Zhuang X (2007) RNAi and microRNA: breakthrough technologies for the improvement of plant nutritional value and metabolic engineering. Metabolomics 3:357–369

    Article  CAS  Google Scholar 

  • Tewari M, Vidal M (2003) RNAi on the apoptosis TRAIL: the mammalian cell genetic screen comes of age. Dev Cell 5:534–535

    Article  PubMed  CAS  Google Scholar 

  • Tomari Y, Matranga C, Haley B, Martinez N, Zamore PD (2004) A protein sensor for siRNA asymmetry. Science 306:1377–1380

    Article  PubMed  CAS  Google Scholar 

  • Townsend BJ, Llewellyn DJ (2007) Reduced terpene levels in cottonseed add food to fiber. Trends Biotechnol 25:239–241

    Article  PubMed  CAS  Google Scholar 

  • Ui-Tei K, Naito Y, Takahashi F, Haraguchi T, Ohki-Hamazaki H, Juni A, Ueda R, Saigo K (2004) Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic Acids Res 32:936–948

    Article  PubMed  CAS  Google Scholar 

  • Ui-Tei K, Naito Y, Zenno S, Nishi K, Yamato K, Takahashi F, Juni A, Saigo K (2008) Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect. Nucleic Acids Res 36:2136–2151

    Article  PubMed  CAS  Google Scholar 

  • 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 Ther 12:461–466

    Article  PubMed  CAS  Google Scholar 

  • Vert JP, Foveau N, Lajaunie C, Vandenbrouck Y (2006) An accurate and interpretable model for siRNA efficacy prediction. BMC Bioinformatics 7:520.

    Article  PubMed  CAS  Google Scholar 

  • Vickers TA, Koo S, Bennett CF, Crooke ST, Dean NM, Baker BF (2003) Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. A comparative analysis. J Biol Chem 278:7108–7118

    Article  PubMed  CAS  Google Scholar 

  • Wakefield DH, Klein JJ, Wolff JA, Rozema DB (2005) Membrane activity and transfection ability of amphipathic polycations as a function of alkyl group size. Bioconjug Chem 16:1204–1208

    Article  PubMed  CAS  Google Scholar 

  • Walton SP, Roth CM, Yarmush ML (2000) Antisense technology. In: The biomedical engineering handbook. CRC Press LLC, Boca Raton, FL, pp 103–119.

    Google Scholar 

  • Warner TG (1999) Enhancing therapeutic glycoprotein production in Chinese hamster ovary cells by metabolic engineering endogenous gene control with antisense DNA and gene targeting. Glycobiology 9:841–850

    Article  PubMed  CAS  Google Scholar 

  • Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727–730.

    Article  PubMed  CAS  Google Scholar 

  • Weitzer S, Martinez J (2007) The human RNA kinase hClp1 is active on 3′ transfer RNA exons and short interfering RNAs. Nature 447:222–226

    Article  PubMed  CAS  Google Scholar 

  • Westerhout EM, Berkhout B (2007) A systematic analysis of the effect of target RNA structure on RNA interference. Nucleic Acids Res 35:4322–4330

    Article  PubMed  CAS  Google Scholar 

  • Wolff JA, Rozema DB (2008) Breaking the bonds: non-viral vectors become chemically dynamic. Mol Ther 16:8–15

    Article  PubMed  CAS  Google Scholar 

  • Wurm FM (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22:1393–1398

    Article  PubMed  CAS  Google Scholar 

  • Yoshinari K, Miyagishi M, Taira K (2004) Effects on RNAi of the tight structure, sequence and position of the targeted region. Nucleic Acids Res 32:691–699

    Article  PubMed  CAS  Google Scholar 

  • Zhang S, Zhao B, Jiang H, Wang B, Ma B (2007) Cationic lipids and polymers mediated vectors for delivery of siRNA. J Control Release 123:1–10

    Article  PubMed  CAS  Google Scholar 

  • Zhu X, Galili G (2004) Lysine metabolism is concurrently regulated by synthesis and catabolism in both reproductive and vegetative tissues. Plant Physiol 135:129–136

    Article  PubMed  CAS  Google Scholar 

  • Zuhorn IS, Engberts JB, Hoekstra D (2007) Gene delivery by cationic lipid vectors: overcoming cellular barriers. Eur Biophys J 36:349–362

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Financial support for this work was provided in part by Michigan State University, the National Science Foundation (#0425821), and the National Institutes of Health (#CA126136, #GM079688, #RR024439).

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Correspondence to S. Patrick Walton .

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Gredell, J.A., Kini, H.K., Walton, S.P. (2009). Engineering Cell Function by RNA Interference. In: Al-Rubeai, M. (eds) Cell Line Development. Cell Engineering, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2245-5_9

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