Delivery of RNAi mediators
Corresponding Author
Lance P. Ford
Bioo Scientific, 3913 Todd Lane Suite 312, Austin, TX 78744, USA
Bioo Scientific, 3913 Todd Lane Suite 312, Austin, TX 78744, USASearch for more papers by this authorMasoud M. Toloue
Bioo Scientific, 3913 Todd Lane Suite 312, Austin, TX 78744, USA
Search for more papers by this authorCorresponding Author
Lance P. Ford
Bioo Scientific, 3913 Todd Lane Suite 312, Austin, TX 78744, USA
Bioo Scientific, 3913 Todd Lane Suite 312, Austin, TX 78744, USASearch for more papers by this authorMasoud M. Toloue
Bioo Scientific, 3913 Todd Lane Suite 312, Austin, TX 78744, USA
Search for more papers by this authorAbstract
Delivering polynucleotides into animals has been a major challenge facing their success as therapeutic agents. Given the matured understanding of antibody-mediated delivery techniques, it is possible to rationally design delivery vehicles that circulate in the blood stream and are specifically delivered into target organs. If the targeting moiety is designed to contain the cargo of an RNAi mediator without impacting its paratope, directed delivery can be achieved. In this article, we review the state of art in delivery technology for RNA mediators and address how this technique could soon be used to enhance the efficacy of the numerous small RNA therapeutic programs currently under evaluation. Copyright © 2010 John Wiley & Sons, Ltd.
This article is categorized under:
- Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action
- RNA Methods > RNA Analyses in Cells
- RNA in Disease and Development > RNA in Disease
REFERENCES
- 1Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998, 391: 806–811.
- 2Han SE, Kang H, Shim GY, Kim SJ, Choi HG, Kim J, Hahn SK, Oh YK. Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides. J Drug Target 2009, 17: 123–132.
- 3Howard KA. Delivery of RNA interference therapeutics using polycation-based nanoparticles. Adv Drug Deliv Rev 2009, 61: 710–720.
- 4Tseng YC, Mozumdar S, Huang L. Lipid-based systemic delivery of siRNA. Adv Drug Deliv Rev 2009, 61: 721–731.
- 5Zhang C, Newsome JT, Mewani R, Pei J, Gokhale PC, Kasid UN. Systemic delivery and pre-clinical evaluation of nanoparticles containing antisense oligonucleotides and siRNAs. Methods Mol Biol 2009, 480: 65–83.
- 6Gao S, Dagnaes-Hansen F, Nielsen EJ, Wengel J, Besenbacher F, Howard KA, Kjems J. The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol Ther 2009, 17: 1225–1233.
- 7Kariko K, Bhuyan P, Capodici J, Ni H, Lubinski J, Friedman H, Weissman D. Exogenous siRNA mediates sequence-independent gene suppression by signaling through toll-like receptor 3. Cells Tissues Organs 2004, 177: 132–138.
- 8Cho WG, Albuquerque RJ, Kleinman ME, Tarallo V, Greco A, Nozaki M, Green MG, Baffi JZ, Ambati BK, De Falco M, et al. Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth. Proc Natl Acad Sci U S A 2009, 106: 7137–7142.
- 9Morrissey DV, Blanchard K, Shaw L, Jensen K, Lockridge JA, Dickinson B, McSwiggen JA, Vargeese C, Bowman K, Shaffer CS, et al. Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 2005, 41: 1349–1356.
- 10Morrissey DV, Lockridge JA, Shaw L, Blanchard K, Jensen K, Breen W, Hartsough K, Machemer L, Radka S, Jadhav V, et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 2005, 23: 1002–1007.
- 11Zimmermann TS, Lee AC, Akinc A, Bramlage B, Bumcrot D, Fedoruk MN, Harborth J, Heyes JA, Jeffs LB, John M, et al. RNAi-mediated gene silencing in non-human primates. Nature 2006, 441: 111–114.
- 12Alshamsan A, Haddadi A, Incani V, Samuel J, Lavasanifar A, Uludag H. Formulation and delivery of siRNA by oleic acid and stearic acid modified polyethylenimine. Mol Pharm 2009, 6: 121–133.
- 13Andersen MO, Howard KA, Kjems J. RNAi using a chitosan/siRNA nanoparticle system: in vitro and in vivo applications. Methods Mol Biol 2009, 555: 77–86.
- 14Subramanian N, Mani P, Roy S, Gnanasundram SV, Sarkar DP, Das S. Targeted delivery of hepatitis C virus-specific short hairpin RNA in mouse liver using Sendai virosomes. J Gen Virol 2009, 90: 1812–1819.
- 15Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R, Donoghue M, Elbashir S, Geick A, Hadwiger P, Harborth J, et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 2004, 432: 173–178.
- 16Manoharan M. RNA interference and chemically modified siRNAs. Nucleic Acids Res Suppl 2003, 3: 115–116.
- 17Manoharan M. RNA interference and chemically modified small interfering RNAs. Curr Opin Chem Biol 2004, 8: 570–579.
- 18Akinc A, Goldberg M, Qin J, Dorkin JR, Gamba-Vitalo C, Maier M, Jayaprakash KN, Jayaraman M, Rajeev KG, Manoharan M, et al. Development of lipidoid-siRNA formulations for systemic delivery to the liver. Mol Ther 2009, 17: 872–879.
- 19Wolfrum C, Shi S, Jayaprakash KN, Jayaraman M, Wang G, Pandey RK, Rajeev KG, Nakayama T, Charrise K, Ndungo EM, et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat Biotechnol 2007, 25: 1149–1157.
- 20Bitko V, Musiyenko A, Shulyayeva O, Barik S. Inhibition of respiratory viruses by nasally administered siRNA. Nat Med 2005, 11: 50–55.
- 21Li BJ, Tang Q, Cheng D, Qin C, Xie FY, Wei Q, Xu J, Liu Y, Zheng BJ, Woodle MC, et al. Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque. Nat Med 2005, 11: 944–951.
- 22Grillot-Courvalin C, Goussard S, Huetz F, Ojcius DM, Courvalin P. Functional gene transfer from intracellular bacteria to mammalian cells. Nat Biotechnol 1998, 16: 862–866.
- 23Palliser D, Chowdhury D, Wang QY, Lee SJ, Bronson RT, Knipe DM, Lieberman J. An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature 2006, 439: 89–94.
- 24Santel A, Aleku M, Keil O, Endruschat J, Esche V, Fisch G, Dames S, Loffler K, Fechtner, M, Arnold W, et al. A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene Ther 2006, 13: 1222–1234.
- 25Xiang S, Fruehauf J, Li CJ. Short hairpin RNA-expressing bacteria elicit RNA interference in mammals. Nat Biotechnol 2006, 24: 697–702.
- 26Yang R, Yang X, Zhang Z, Zhang Y, Wang S, Cai Z, Jia Y, Ma Y, Zheng C, Lu Y, et al. Single-walled carbon nanotubes-mediated in vivo and in vitro delivery of siRNA into antigen-presenting cells. Gene Ther 2006, 13: 1714–1723.
- 27Agrawal A, Min DH, Singh N, Zhu H, Birjiniuk A, von Maltzahn G, Harris TJ, Xing D, Woolfenden SD, Sharp PA, et al. Functional delivery of siRNA in mice using dendriworms. ACS Nano 2009, 3: 2495–2504.
- 28Mathupala SP. Delivery of small-interfering RNA (siRNA) to the brain. Expert Opin Ther Pat 2009, 19: 137–140.
- 29Pardridge WM. Intravenous, non-viral RNAi gene therapy of brain cancer. Expert Opin Biol Ther 2004, 4: 1103–1113.
- 30Reimer DL, Zhang Y, Kong S, Wheeler JJ, Graham RW, Bally MB. Formation of novel hydrophobic complexes between cationic lipids and plasmid DNA. Biochemistry 1995, 34: 12877–12883.
- 31Huang L, Li S. Liposomal gene delivery: a complex package. Nat Biotechnol 1997, 15: 620–621.
- 32Mahato RI, Rolland A, Tomlinson E. Cationic lipid-based gene delivery systems: pharmaceutical perspectives. Pharm Res 1997, 14: 853–859.
- 33Matsui H, Johnson LG, Randell SH, Boucher RC. Loss of binding and entry of liposome-DNA complexes decreases transfection efficiency in differentiated airway epithelial cells. J Biol Chem 1997, 272: 1117–1126.
- 34Huwyler J, Wu D, Pardridge WM. Brain drug delivery of small molecules using immunoliposomes. Proc Natl Acad Sci U S A 1996, 93: 14164–14169.
- 35Xia CF, Zhang Y, Boado RJ, Pardridge WM. Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology. Pharm Res 2007, 24: 2309–2316.
- 36Whelan J. Beyond PEGylation. Drug Discov Today 2005, 10: 301.
- 37Whelan J. First clinical data on RNAi. Drug Discov Today 2005, 10: 1014–1015.
- 38Tolentino MJ, Brucker AJ, Fosnot J, Ying GS, Wu IH, Malik G, Wan S, Reich SJ. Intravitreal injection of vascular endothelial growth factor small interfering RNA inhibits growth and leakage in a nonhuman primate, laser-induced model of choroidal neovascularization. Retina 2004, 24: 660.
- 39Reich SJ, Fosnot J, Kuroki A, Tang W, Yang X, Maguire AM, Bennett J, Tolentino MJ. Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model. Mol Vis 2003, 9: 210–216.
- 40Nakamura H, Siddiqui SS, Shen X, Malik AB, Pulido JS, Kumar NM, Yue BY. RNA interference targeting transforming growth factor-beta type II receptor suppresses ocular inflammation and fibrosis. Mol Vis 2004, 10: 703–711.
- 41Singerman L. Combination therapy using the small interfering RNA bevasiranib. Retina 2009, 29(Suppl 6): S49–S50.
- 42Kleinman ME, Yamada K, Takeda A, Chandrasekaran V, Nozaki M, Baffi JZ, Albuquerque RJ, Yamasaki S, Itaya M, Pan Y, et al. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 2008, 452: 591–597.
- 43Barik S. Development of gene-specific double-stranded RNA drugs. Ann Med 2004, 36: 540–551.
- 44Barik S. Treating respiratory viral diseases with chemically modified, second generation intranasal siRNAs. Methods Mol Biol 2009, 487: 331–341.
- 45Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE. RNA interference targeting the M2 subunit of ribonucleotide reductase enhances pancreatic adenocarcinoma chemosensitivity to gemcitabine. Oncogene 2004, 23: 1539–1548.
- 46Xu L, Huang CC, Huang W, Tang WH, Rait A, Yin YZ, Cruz I, Xiang LM, Pirollo KF, Chang EH. Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes. Mol Cancer Ther 2002, 1: 337–346.
- 47Kovar H, Ban J, Pospisilova S. Potentials for RNAi in sarcoma research and therapy: Ewing's sarcoma as a model. Semin Cancer Biol 2003, 13: 275–281.
- 48Davis ME. The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol Pharm 2009, 6: 659–668.
- 49Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. Silencing of microRNAs in vivo with ‘antagomirs’ Nature 2005, 483: 685–689..
10.1038/nature04303 Google Scholar
- 50Pappas TC, Bader AG, Andruss BF, Brown D, Ford LP. Applying small RNA molecules to the directed treatment of human diseases: realizing the potential. Expert Opin Ther Targets 2008, 12: 115–127.
- 51Blackburn WH, Dickerson EB, Smith MH, McDonald JF, Lyon LA. Peptide-functionalized nanogels for targeted siRNA delivery. Bioconjug Chem 2009, 20: 960–968.
- 52Jeong JH, Mok H, Oh YK, Park TG. siRNA conjugate delivery systems. Bioconjug Chem 2009, 20: 5–14.
- 53Wullner U, Neef I, Tur MK, Barth S. Targeted delivery of short interfering RNAs–strategies for in vivo delivery. Recent Pat Anticancer Drug Discov 2009, 4: 1–8.
- 54Yu B, Zhao X, Lee LJ, Lee RJ. Targeted delivery systems for oligonucleotide therapeutics. AAPS J 2009, 11: 195–203.
- 55Zheng X, Vladau C, Zhang X, Suzuki M, Ichim TE, Zhang ZX, Li M, Carrier E, Garcia B, Jevnikar AM, et al. A novel in vivo siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation. Blood 2009, 113: 2646–2654.
- 56Lorenz C, Hadwiger P, John M, Vornlocher HP, Unverzagt C. Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells. Bioorg Med Chem Lett 2004, 14: 4975–4977.
- 57Wang XL, Xu R, Lu ZR. A peptide-targeted delivery system with pH-sensitive amphiphilic cell membrane disruption for efficient receptor-mediated siRNA delivery. J Control Release 2009, 134: 207–213.
- 58Pirollo KF, Chang EH. Targeted delivery of small interfering RNA: approaching effective cancer therapies. Cancer Res 2008, 68: 1247–1250.
- 59Pirollo KF, Rait A, Zhou Q, Hwang SH, Dagata JA, Zon G, Hogrefe RI, Palchik G, Chang EH. Materializing the potential of small interfering RNA via a tumor-targeting nanodelivery system. Cancer Res 2007, 67: 2938–2943.
- 60Pirollo KF, Zon G, Rait A, Zhou Q, Yu W, Hogrefe R, Chang EH. Tumor-targeting nanoimmunoliposome complex for short interfering RNA delivery. Hum Gene Ther 2006, 17: 117–124.
- 61Song E, Zhu P, Lee SK, Chowdhury D, Kussman S, Dykxhoorn DM, Feng Y, Palliser D, Weiner DB, Shankar P, et al. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol 2005, 23: 709–717.
- 62Kumar P, Ban HS, Kim SS, Wu H, Pearson T, Greiner DL, Laouar A, Yao J, Haridas V, Habiro K, et al. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 2008, 134: 577–586.
- 63Tuschl T, Zamore PD, Lehmann R, Bartel DP, Sharp PA. Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev 1999, 13: 3191–3197.
- 64Parrish S, Fleenor J, Xu S, Mello C, Fire A. Functional anatomy of a dsRNA trigger: differential requirement for the two trigger strands in RNA interference. Mol Cell 2000, 6: 1077–1087.
- 65Zamore PD, Tuschl T, Sharp PA, Bartel DP. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 2000, 101: 25–33.
- 66Elbashir SM, Lendeckel W, Tuschl T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 2001, 15: 188–200.
- 67Peer D, Zhu P, Carman CV, Lieberman J, Shimaoka M. Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1. Proc Natl Acad Sci U S A 2007, 104: 4095–4100.
- 68Liu Z, Winters M, Holodniy M, Dai H. siRNA delivery into human T cells and primary cells with carbon-nanotube transporters. Angew Chem Int Ed Engl 2007, 46: 2023–2027.
- 69Duffy MJ. Predictive markers in breast and other cancers: a review. Clin Chem 2005, 51: 494–503.
- 70Ono M, Kuwano M. Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and response to gefitinib and other EGFR-targeting drugs. Clin Cancer Res 2006, 12: 7242–7251.
- 71Meden H, Kuhn W. Overexpression of the oncogene c-erbB-2 (HER2/neu) in ovarian cancer: a new prognostic factor. Eur J Obstet Gynecol Reprod Biol 1997, 71: 173–179.
- 72Dykxhoorn DM, Lieberman J. The silent revolution: RNA interference as basic biology, research tool, and therapeutic. Annu Rev Med 2005, 56: 401–423.
- 73Schiffelers RM, Ansari A, Xu J, Zhou Q, Tang Q, Storm G, Molema G, Lu PY, Scaria PV, Woodle MC. Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Res 2004, 32: e149.
- 74Kim SH, Mok H, Jeong JH, Kim SW, Park TG. Comparative evaluation of target-specific GFP gene silencing efficiencies for antisense ODN, synthetic siRNA, and siRNA plasmid complexed with PEI-PEG-FOL conjugate. Bioconjug Chem 2006, 17: 241–244.
- 75Peer D, Park EJ, Morishita Y, Carman CV, Shimaoka M. Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science 2008, 319: 627–630.
- 76Daniels TR, Delgado T, Helguera G, Penichet ML. The transferrin receptor part II: targeted delivery of therapeutic agents into cancer cells. Clin Immunol 2006, 121: 159–176.
- 77Daniels TR, Delgado T, Rodriguez JA, Helguera G, Penichet ML. The transferrin receptor part I: biology and targeting with cytotoxic antibodies for the treatment of cancer. Clin Immunol 2006, 121: 144–158.
- 78Chen QR, Zhang L, Luther PW, Mixson AJ. Optimal transfection with the HK polymer depends on its degree of branching and the pH of endocytic vesicles. Nucleic Acids Res 2002, 30: 1338–1345.
- 79Aoki Y, Hosaka S, Kawa S, Kiyosawa K. Potential tumor-targeting peptide vector of histidylated oligolysine conjugated to a tumor-homing RGD motif. Cancer Gene Ther 2001, 8: 783–787.