366
Views
29
CrossRef citations to date
0
Altmetric
Reviews

Delivery of RNAi therapeutics: work in progress

Pages 781-811 | Published online: 09 Jan 2014

References

  • Dykxhoorn DM. RNA interference as an anticancer therapy: a patent perspective. Expert Opin. Ther. Pat. 19(4), 475–491 (2009).
  • Dykxhoorn DM, Lieberman J. The silent revolution: RNA interference as basic biology, research tool, and therapeutic. Annu. Rev. Med. 56, 401–423 (2005).
  • Dykxhoorn DM, Lieberman J. Knocking down disease with siRNAs. Cell 126(2), 231–235 (2006).
  • Dykxhoorn DM, Lieberman J. Running interference: prospects and obstacles to using small interfering RNAs as small molecule drugs. Annu. Rev. Biomed. Eng. 8, 377–402 (2006).
  • Dykxhoorn DM, Palliser D, Lieberman J. The silent treatment: siRNAs as small molecule drugs. Gene. Ther. 13(6), 541–552 (2006).
  • de Fougerolles A, Vornlocher HP, Maraganore J, Lieberman J. Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug. Discov. 6(6), 443–453 (2007).
  • Tripp RA, Tompkins SM. Therapeutic applications of RNAi for silencing virus replication. Methods Mol. Biol. 555, 43–61 (2009).
  • Bratkovic T, Rogelj B. Biology and applications of small nucleolar RNAs. Cell Mol. Life Sci. 68(23), 3843–3851 (2011).
  • Collins LJ. Characterizing ncRNAs in human pathogenic protists using high-throughput sequencing technology. Front. Genet. 2, 96 (2011).
  • Holley CL, Topkara VK. An introduction to small non-coding RNAs: miRNA and snoRNA. Cardiovasc. Drugs Ther. 25(2), 151–159 (2011).
  • Makarova JA, Kramerov DA. SNOntology: Myriads of Novel SnoRNAs or Just a Mirage? BMC genomics. 12(1), 543 (2011).
  • Scott MS, Ono M. From snoRNA to miRNA: Dual function regulatory non-coding RNAs. Biochimie 93(11), 1987–1992 (2011).
  • Esteller M. Non-coding RNAs in human disease. Nat. Rev. Genet. 12(12), 861–874 (2011).
  • Tsujiuchi T, Wakabayashi T, Miller AD, Natsume A. RNA interference therapeutics for tumour therapy: promising work in progress. In: Gene Therapy of Cancer (3rd Edition). Lattime, EC, Gerson, SL ( Eds). Academic Press, MA, USA 2013.
  • Li F, Pallan PS, Maier MA et al. Crystal structure, stability and in vitro RNAi activity of oligoribonucleotides containing the ribo-difluorotoluyl nucleotide: insights into substrate requirements by the human RISC Ago2 enzyme. Nucleic Acids Res. 35(19), 6424–6438 (2007).
  • Ui-Tei K, Naito Y, Nishi K, Juni A, Saigo K. Thermodynamic stability and Watson-Crick base pairing in the seed duplex are major determinants of the efficiency of the siRNA-based off-target effect. Nucleic Acids Res. 36(22), 7100–7109 (2008).
  • Ui-Tei K, Naito Y, Saigo K. Essential notes regarding the design of functional siRNAs for efficient mammalian RNAi. J. Biomed. Biotechnol. 65052 (2006).
  • Kostarelos K, Miller AD. Synthetic, self-assembly ABCD nanoparticles; a structural paradigm for viable synthetic non-viral vectors. Chem. Soc. Rev. 34(11), 970–994 (2005).
  • Kurreck J. RNA interference: from basic research to therapeutic applications. Angew. Chem. Int. Ed. Engl. 48(8), 1378–1398 (2009).
  • Miller AD. Towards safe nanoparticle technologies for nucleic acid therapeutics. Tumori 94(2), 234–245 (2008).
  • Akhtar S, Benter IF. Nonviral delivery of synthetic siRNAs in vivo. J. Clin. Invest. 117(12), 3623–3632 (2007).
  • De Paula D, Bentley MV, Mahato RI. Hydrophobization and bioconjugation for enhanced siRNA delivery and targeting. RNA 13(4), 431–456 (2007).
  • Gao K, Huang L. Nonviral methods for siRNA delivery. Mol. Pharm. 6(3), 651–658 (2009).
  • Tseng YC, Mozumdar S, Huang L. Lipid-based systemic delivery of siRNA. Adv. Drug Deliv. Rev. 61(9), 721–731 (2009).
  • Hickerson RP, Vlassov AV, Wang Q et al. Stability study of unmodified siRNA and relevance to clinical use. Oligonucleotides 18(4), 345–354 (2008).
  • Morin A, Gallou-Kabani C, Mathieu JR, Cabon F. Systemic delivery and quantification of unformulated interfering RNAs in vivo. Curr. Top. Med. Chem. 9(12), 1117–1129 (2009).
  • Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 8(2), 129–138 (2009).
  • Fattal E, Bochot A. Ocular delivery of nucleic acids: antisense oligonucleotides, aptamers and siRNA. Adv. Drug Deliv. Rev. 58(11), 1203–1223 (2006).
  • Pardridge WM. Intravenous, non-viral RNAi gene therapy of brain cancer. Expert Opin. Biol. Ther. 4(7), 1103–1113 (2004).
  • Pardridge WM. shRNA and siRNA delivery to the brain. Adv. Drug Deliv. Rev. 59(2–3), 141–152 (2007).
  • Mathupala SP. Delivery of small-interfering RNA (siRNA) to the brain. Expert Opin. Ther. Pat. 19(2), 137–140 (2009).
  • Akhtar S. Oral delivery of siRNA and antisense oligonucleotides. J. Drug Target 17(7), 491–495 (2009).
  • Jain KK. Stability and delivery of RNA via the gastrointestinal tract. Curr. Drug Deliv. 5(1), 27–31 (2008).
  • Tang Q, Li B, Woodle M, Lu PY. Application of siRNA against SARS in the rhesus macaque model. Methods Mol. Biol. 442, 139–158 (2008).
  • Cheng K, Mahato RI. siRNA delivery and targeting. Mol. Pharm. 6(3), 649–650 (2009).
  • Fattal E, Bochot A. State of the art and perspectives for the delivery of antisense oligonucleotides and siRNA by polymeric nanocarriers. Int. J. Pharm. 364(2), 237–248 (2008).
  • Fenske DB, Chonn A, Cullis PR. Liposomal nanomedicines: an emerging field. Toxicol. Pathol. 36(1), 21–29 (2008).
  • Fenske DB, Cullis PR. Liposomal nanomedicines. Expert Opin. Drug Deliv. 5(1), 25–44 (2008).
  • Li SD, Huang L. Targeted delivery of siRNA by nonviral vectors: lessons learned from recent advances. Curr. Opin. Investig. Drugs 9(12), 1317–1323 (2008).
  • Li W, Szoka FC, Jr. Lipid-based nanoparticles for nucleic acid delivery. Pharm. Res. 24(3), 438–449 (2007).
  • Philipp A, Meyer M, Wagner E. Extracellular targeting of synthetic therapeutic nucleic acid formulations. Curr. Gene. Ther. 8(5), 324–334 (2008).
  • Wu SY, McMillan NA. Lipidic Systems for In Vivo siRNA Delivery. AAPS J. 11(4), 639–652 (2009).
  • Jeong JH, Mok H, Oh YK, Park TG. siRNA conjugate delivery systems. Bioconjug. Chem. 20(1), 5–14 (2009).
  • Jere D, Arote R, Jiang HL, Kim YK, Cho MH, Cho CS. Bioreducible polymers for efficient gene and siRNA delivery. Biomed. Mater. 4(2), 25020 (2009).
  • Kim SS, Garg H, Joshi A, Manjunath N. Strategies for targeted nonviral delivery of siRNAs in vivo. Trends Mol. Med. 15(11), 491–500 (2009).
  • Miller AD. Synthetic nucleic acid delivery systems in gene therapy. In: Encyclopedia of Life Sciences. J. Wiley & Sons, NJ, USA (2008)
  • Thanou M, Waddington S, Miller AD. Gene Therapy. In: Comprehensive Medicinal Chemistry II. Taylor, JB, Triggle, DJ ( Eds). Elsevier, Oxford, UK 297–320 (2007).
  • Miller AD. The problem with cationic liposome/micelle-based non-viral vector systems for gene therapy. Curr. Med. Chem. 10(14), 1195–1211 (2003).
  • Mangala LS, Han HD, Lopez-Berestein G, Sood AK. Liposomal siRNA for ovarian cancer. Methods Mol. Biol. 555, 29–42 (2009).
  • Villares GJ, Zigler M, Wang H et al. Targeting melanoma growth and metastasis with systemic delivery of liposome-incorporated protease-activated receptor-1 small interfering RNA. Cancer Res. 68(21), 9078–9086 (2008).
  • Mével M, Kamaly N, Carmona S et al. DODAG; a versatile new cationic lipid that mediates efficient delivery of pDNA and siRNA. J. Control Rel. 143(2), 222–232 (2010).
  • Khoury M, Jorgensen C, Apparailly F. RNAi in arthritis: prospects of a future antisense therapy in inflammation. Curr. Opin. Mol. Ther. 9(5), 483–489 (2007).
  • Khoury M, Louis-Plence P, Escriou V et al. Efficient new cationic liposome formulation for systemic delivery of small interfering RNA silencing tumor necrosis factor alpha in experimental arthritis. Arthritis. Rheum. 54(6), 1867–1877 (2006).
  • Pal A, Ahmad A, Khan S et al. Systemic delivery of Raf-siRNA using cationic cardiolipin liposomes silences Raf-1 expression and inhibits tumor growth in xenograft model of human prostate cancer. Int. J. Oncol. 26(4), 1087–1091 (2005).
  • Guissouma H, Froidevaux MS, Hassani Z, Demeneix BA. In vivo siRNA delivery to the mouse hypothalamus confirms distinct roles of TR beta isoforms in regulating TRH transcription. Neurosci. Lett. 406(3), 240–243 (2006).
  • Hassani Z, Lemkine GF, Erbacher P et al. Lipid-mediated siRNA delivery down-regulates exogenous gene expression in the mouse brain at picomolar levels. J. Gene. Med. 7(2), 198–207 (2005).
  • Zhang 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. 480, 65–83 (2009).
  • Dore-Savard L, Roussy G, Dansereau MA et al. Central delivery of Dicer-substrate siRNA: a direct application for pain research. Mol. Ther. 16(7), 1331–1339 (2008).
  • Kim SI, Shin D, Choi TH et al. Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I. Mol. Ther. 15(6), 1145–1152 (2007).
  • Kim SI, Shin D, Lee H, Ahn BY, Yoon Y, Kim M. Targeted delivery of siRNA against hepatitis C virus by apolipoprotein A-I-bound cationic liposomes. J. Hepatol. 50(3), 479–488 (2009).
  • Lee H, Kim SI, Shin D et al. Hepatic siRNA delivery using recombinant human apolipoprotein A-I in mice. Biochem. Biophys. Res. Commun. 378(2), 192–196 (2009).
  • Hogrefe RI, Lebedev AV, Zon G et al. Chemically modified short interfering hybrids (siHYBRIDS): nanoimmunoliposome delivery in vitro and in vivo for RNAi of HER-2. Nucleosides Nucleotides Nucleic Acids 25(8), 889–907 (2006).
  • Pirollo KF, Zon G, Rait A et al. Tumor-targeting nanoimmunoliposome complex for short interfering RNA delivery. Hum. Gene. Ther. 17(1), 117–124 (2006).
  • Pirollo KF, Chang EH. Targeted delivery of small interfering RNA: approaching effective cancer therapies. Cancer Res. 68(5), 1247–1250 (2008).
  • Pirollo KF, Rait A, Zhou Q et al. Materializing the potential of small interfering RNA via a tumor-targeting nanodelivery system. Cancer Res. 67(7), 2938–2943 (2007).
  • Zheng X, Vladau C, Zhang X et al. A novel in vivo siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation. Blood 113(12), 2646–2654 (2009).
  • de Jonge J, Holtrop M, Wilschut J, Huckriede A. Reconstituted influenza virus envelopes as an efficient carrier system for cellular delivery of small-interfering RNAs. Gene. Ther. 13(5), 400–411 (2006).
  • Kunisawa J, Masuda T, Katayama K et al. Fusogenic liposome delivers encapsulated nanoparticles for cytosolic controlled gene release. J. Control Rel. 105(3), 344–353 (2005).
  • Matsuda M, Yamamoto T, Matsumura A, Kaneda Y. Highly efficient eradication of intracranial glioblastoma using Eg5 siRNA combined with HVJ envelope. Gene. Ther. 16(12), 1465–1476 (2009).
  • Subramanian 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. 90(Pt 8), 1812–1819 (2009).
  • Sato A, Takagi M, Shimamoto A, Kawakami S, Hashida M. Small interfering RNA delivery to the liver by intravenous administration of galactosylated cationic liposomes in mice. Biomaterials 28(7), 1434–1442 (2007).
  • Watanabe T, Umehara T, Yasui F et al. Liver target delivery of small interfering RNA to the HCV gene by lactosylated cationic liposome. J. Hepatol. 47(6), 744–750 (2007).
  • Zhang YP, Sekirov L, Saravolac EG et al. Stabilized plasmid-lipid particles for regional gene therapy: formulation and transfection properties. Gene. Ther. 6(8), 1438–1447 (1999).
  • Wheeler JJ, Palmer L, Ossanlou M et al. Stabilized plasmid-lipid particles: construction and characterization. Gene. Ther. 6(2), 271–281 (1999).
  • Mok KW, Lam AM, Cullis PR. Stabilized plasmid-lipid particles: factors influencing plasmid entrapment and transfection properties. Biochim. Biophys. Acta 1419(2), 137–150 (1999).
  • Morrissey DV, Lockridge JA, Shaw L et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat. Biotechnol. 23(8), 1002–1007 (2005).
  • Zimmermann TS, Lee AC, Akinc A et al. RNAi-mediated gene silencing in non-human primates. Nature 441(7089), 111–114 (2006).
  • Semple SC, Akinc A, Chen J et al. Rational design of cationic lipids for siRNA delivery. Nat. Biotechnol. 28(2), 172–176 (2010).
  • Basha G, Novobrantseva TI, Rosin N et al. Influence of cationic lipid composition on gene silencing properties of lipid nanoparticle formulations of sirna in antigen-presenting cells. Mol. Ther. 19(12), 2186–2200 (2011).
  • Lee JB, Zhang K, Tam YY et al. Lipid nanoparticle siRNA systems for silencing the androgen receptor in human prostate cancer in vivo. Int. J. Cancer 131(5), E781–E790 (2011).
  • Jayaraman M, Ansell SM, Mui BL et al. Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo. Angew. Chem. Int. Ed. Engl. 51(34), 8529–8533 (2012).
  • Abrams MT, Koser ML, Seitzer J et al. Evaluation of efficacy, biodistribution, and inflammation for a potent siRNA nanoparticle: effect of dexamethasone co-treatment. Mol. Ther. 18(1), 171–180 (2010).
  • Crawford R, Dogdas B, Keough E et al. Analysis of lipid nanoparticles by Cryo-EM for characterizing siRNA delivery vehicles. Int. J. Pharm. 403(1–2), 237–244 (2011).
  • Pei Y, Hancock PJ, Zhang H et al. Quantitative evaluation of siRNA delivery in vivo. RNA 16(12), 2553–2563 (2010).
  • Tao W, Mao X, Davide JP et al. Mechanistically probing lipid-siRNA nanoparticle-associated toxicities identifies Jak inhibitors effective in mitigating multifaceted toxic responses. Mol. Ther. 19(3), 567–575 (2011).
  • Santel A, Aleku M, Keil O et al. RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy. Gene. Ther. 13(18), 1360–1370 (2006).
  • Santel A, Aleku M, Keil O et al. A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene. Ther. 13(16), 1222–1234 (2006).
  • Aleku M, Schulz P, Keil O et al. Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression. Cancer Res. 68(23), 9788–9798 (2008).
  • Adami RC, Seth S, Harvie P et al. An amino acid-based amphoteric liposomal delivery system for systemic administration of siRNA. Mol. Ther. 19(6), 1141–1151 (2011).
  • Sonoke S, Ueda T, Fujiwara K et al. Tumor regression in mice by delivery of Bcl-2 small interfering RNA with pegylated cationic liposomes. Cancer Res. 68(21), 8843–8851 (2008).
  • Frank-Kamenetsky M, Grefhorst A, Anderson NN et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc. Natl Acad. Sci. U.S.A. 105(33), 11915–11920 (2008).
  • Akinc A, Goldberg M, Qin J et al. Development of lipidoid-siRNA formulations for systemic delivery to the liver. Mol. Ther. 17(5), 872–879 (2009).
  • Akinc A, Zumbuehl A, Goldberg M et al. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat. Biotechnol. 26(5), 561–569 (2008).
  • Love KT, Mahon KP, Levins CG et al. Lipid-like materials for low-dose, in vivo gene silencing. Proc. Natl Acad. Sci. U.S.A. 107(5), 1864–1869 (2010).
  • Yoshizawa T, Hattori Y, Hakoshima M, Koga K, Maitani Y. Folate-linked lipid-based nanoparticles for synthetic siRNA delivery in KB tumor xenografts. Eur. J. Pharm. Biopharm. 70(3), 718–725 (2008).
  • Li SD, Huang L. Surface-modified LPD nanoparticles for tumor targeting. Ann. N.Y. Acad. Sci, 1082, 1–8 (2006).
  • Li SD, Huang L. Targeted delivery of antisense oligodeoxynucleotide and small interference RNA into lung cancer cells. Mol. Pharm. 3(5), 579–588 (2006).
  • Chono S, Li SD, Conwell CC, Huang L. An efficient and low immunostimulatory nanoparticle formulation for systemic siRNA delivery to the tumor. J. Control Rel. 131(1), 64–69 (2008).
  • Chen Y, Sen J, Bathula SR, Yang Q, Fittipaldi R, Huang L. Novel cationic lipid that delivers siRNA and enhances therapeutic effect in lung cancer cells. Mol. Pharm. 6(3), 696–705 (2009).
  • Li SD, Huang L. Nanoparticles evading the reticuloendothelial system: role of the supported bilayer. Biochim. Biophys. Acta 1788(10), 2259–2266 (2009).
  • Peer D, Park EJ, Morishita Y, Carman CV, Shimaoka M. Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science 319(5863), 627–630 (2008).
  • Peer D, Shimaoka M. Systemic siRNA delivery to leukocyte-implicated diseases. Cell Cycle 8(6), 853–859 (2009).
  • Srinivasan C, Peer D, Shimaoka M. Integrin-targeted stabilized nanoparticles for an efficient delivery of siRNAs in vitro and in vivo. Methods Mol. Biol. 820, 105–116 (2012).
  • Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J. Control. Rel. 65(1–2), 271–284 (2000).
  • Kong HJ, Mooney DJ. Microenvironmental regulation of biomacromolecular therapies. Nat. Rev. Drug Discov. 6(6), 455–463 (2007).
  • Medina-Kauwe LK, Xie J, Hamm-Alvarez S. Intracellular trafficking of nonviral vectors. Gene. Ther. 12(24), 1734–1751 (2005).
  • Miller AD. Nonviral delivery systems for gene therapy. In: Understanding Gene Therapy. Lemoine NR ( Ed.). Bios Scientific Publishers, Oxford, UK, 43–69 (1999).
  • Serresi M, Bizzarri R, Cardarelli F, Beltram F. Real-time measurement of endosomal acidification by a novel genetically encoded biosensor. Anal. Bioanal. Chem. 393(4), 1123–1133 (2009).
  • Carmona S, Jorgensen MR, Kolli S et al. Controlling HBV replication in vivo by intravenous administration of triggered PEGylated siRNA-nanoparticles. Mol. Pharm. 6(3), 706–717 (2009).
  • Kolli S, Wong SP, Harbottle R, Johnston B, Thanou M, Miller AD. pH-triggered nanoparticle mediated delivery of siRNA to liver cells in vitro and in vivo. Bioconjug. Chem. 24(3), 314–332 (2013).
  • Kenny GD, Kamaly N, Kalber TL et al. Novel multifunctional nanoparticle mediates siRNA tumour delivery, visualisation and therapeutic tumour reduction in vivo. J. Control Rel. 149(2), 111–116 (2011).
  • Aissaoui A, Chami M, Hussein M, Miller AD. Efficient topical delivery of plasmid DNA to lung in vivo mediated by putative triggered, PEGylated pDNA nanoparticles. J. Control Rel. 154(3), 275–284 (2011).
  • Kamaly N, Kalber T, Ahmad A et al. Bimodal paramagnetic and fluorescent liposomes for cellular and tumor magnetic resonance imaging. Bioconjug. Chem. 19(1), 118–129 (2008).
  • Kamaly N, Kalber T, Thanou M, Bell JD, Miller AD. Folate receptor targeted bimodal liposomes for tumor magnetic resonance imaging. Bioconjug. Chem. 20(4), 648–655 (2009).
  • Kamaly N, Kalber T, Kenny G, Bell J, Jorgensen M, Miller A. A novel bimodal lipidic contrast agent for cellular labelling and tumour MRI. Org. Biomol. Chem. 8(1), 201–211 (2010).
  • Drake CR, Aissaoui A, Argyros O, Thanou M, Steinke JH, Miller AD. Examination of the effect of increasing the number of intra-disulfide amino functional groups on the performance of small molecule cyclic polyamine disulfide vectors. J. Control Rel. 171(1), 81–90 (2013).
  • Stewart L, Manvell M, Hillery E et al. Physico-chemical analysis of cationic liposome-DNA complexes (lipoplexes) with respect to in vitro and in vivo gene delivery efficiency. J. Chem. Soc. Perkin Trans. 2 624–632 (2001).
  • Chen J, Jorgensen MR, Thanou M, Miller AD. Post-coupling strategy enables true receptor-targeted nanoparticles. J. RNAi Gene Silencing 7, 449–455 (2011).
  • Wang M, Lowik DW, Miller AD, Thanou M. Targeting the urokinase plasminogen activator receptor with synthetic self-assembly nanoparticles. Bioconjug. Chem. 20(1), 32–40 (2009).
  • Wang M, Miller AD, Thanou M. Effect of surface charge and ligand organization on the specific cell-uptake of uPAR-targeted nanoparticles. J. Drug Target. 21(7), 684–692 (2013).
  • Glaser PE, Gross RW. Plasmenylethanolamine facilitates rapid membrane fusion: a stopped-flow kinetic investigation correlating the propensity of a major plasma membrane constituent to adopt an HII phase with its ability to promote membrane fusion. Biochemistry 33(19), 5805–5812 (1994).
  • Hope MJ, Cullis PR. The role of nonbilayer lipid structures in the fusion of human erythrocytes induced by lipid fusogens. Biochim. Biophys. Acta 640(1), 82–90 (1981).
  • Koltover I, Salditt T, Radler JO, Safinya CR. An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science 281(5373), 78–81 (1998).
  • Fletcher S, Ahmad A, Price WS, Jorgensen MR, Miller AD. Biophysical properties of CDAN/DOPE-analogue lipoplexes account for enhanced gene delivery. ChemBioChem 9(3), 455–463 (2008).
  • Koynova R, Wang L, MacDonald RC. An intracellular lamellar-nonlamellar phase transition rationalizes the superior performance of some cationic lipid transfection agents. Proc. Natl Acad. Sci. U.S.A. 103(39), 14373–14378 (2006).
  • Fletcher S, Ahmad A, Perouzel E, Heron A, Miller AD, Jorgensen MR. In vivo studies of dialkynoyl analogues of DOTAP demonstrate improved gene transfer efficiency of cationic liposomes in mouse lung. J. Med. Chem. 49, 349–357 (2006).
  • Fletcher S, Ahmad A, Perouzel E, Jorgensen MR, Miller AD. A dialkanoyl analogue of DOPE improves gene transfer of lower-charged, cationic lipoplexes. Org. Biomol. Chem. 4, 196–199 (2006).
  • Martin B, Sainlos M, Aissaoui A et al. The design of cationic lipids for gene delivery. Curr. Pharm. Des. 11(3), 375–394 (2005).
  • Keller M, Jorgensen MR, Perouzel E, Miller AD. Thermodynamic aspects and biological profile of CDAN/DOPE and DC-Chol/DOPE lipoplexes. Biochemistry 42(20), 6067–6077 (2003).
  • Huang L, Liu Y. In Vivo Delivery of RNAi with Lipid-Based Nanoparticles. Annu. Rev. Biomed. Eng. 13, 507–530 (2011).
  • Miller AD. Cationic liposomes for gene therapy. Angew. Chem. Int. Ed. 37, 1768–1785 (1998).
  • Bisgaier CL, Siebenkas MV, Williams KJ. Effects of apolipoproteins A-IV and A-I on the uptake of phospholipid liposomes by hepatocytes. J. Biol. Chem. 264(2), 862–866 (1989).
  • Keller M, Harbottle RP, Perouzel E et al. Nuclear localisation sequence templated nonviral gene delivery vectors: investigation of intracellular trafficking events of LMD and LD vector systems. ChemBioChem 4(4), 286–298 (2003).
  • Lu JJ, Langer R, Chen J. A novel mechanism is involved in cationic lipid-mediated functional siRNA delivery. Mol. Pharm. 6(3), 763–771 (2009).
  • Spagnou S, Miller AD, Keller M. Lipidic Carriers of siRNA: Differences in the Formulation, Cellular Uptake, and Delivery with Plasmid DNA. Biochemistry 43(42), 13348–13356 (2004).
  • Zabner J, Fasbender AJ, Moninger T, Poellinger KA, Welsh MJ. Cellular and molecular barriers to gene transfer by a cationic lipid. J. Biol. Chem. 270(32), 18997–19007 (1995).
  • Chiu YL, Ali A, Chu CY, Cao H, Rana TM. Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells. Chem. Biol. 11(8), 1165–1175 (2004).
  • Guo X, Szoka FC, Jr. Steric stabilization of fusogenic liposomes by a low-pH sensitive PEG--diortho ester--lipid conjugate. Bioconjug. Chem. 12(2), 291–300 (2001).
  • Walker GF, Fella C, Pelisek J et al. Toward synthetic viruses: endosomal pH-triggered deshielding of targeted polyplexes greatly enhances gene transfer in vitro and in vivo. Mol. Ther. 11(3), 418–425 (2005).
  • Mudhakir D, Akita H, Tan E, Harashima H. A novel IRQ ligand-modified nano-carrier targeted to a unique pathway of caveolar endocytic pathway. J. Control. Rel. 125(2), 164–173 (2008).
  • Hatakeyama H, Ito E, Akita H et al. A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo. J. Control Rel. 139(2), 127–132 (2009).
  • Hatakeyama H, Akita H, Kogure K et al. Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid. Gene. Ther. 14(1), 68–77 (2007).
  • Zhang JX, Zalipsky S, Mullah N, Pechar M, Allen TM. Pharmaco attributes of dioleoylphosphatidylethanolamine/cholesterylhemisuccinate liposomes containing different types of cleavable lipopolymers. Pharmacol. Res. 49(2), 185–198 (2004).
  • Yingyuad P, Mevel M, Prata C et al. Enzyme-Triggered PEGylated pDNA-Nanoparticles for Controlled Release of pDNA in Tumors. Bioconjug. Chem. 24(3), 343–362 (2013).
  • Drake CR, Aissaoui A, Argyros O et al. Bioresponsive small molecule polyamines as non-cytotoxic alternative to polyethylenimine. Mol. Pharm. 7(6), 2040–2055 (2010).
  • Zalipsky S, Qazen M, Walker JA, 2nd, Mullah N, Quinn YP, Huang SK. New detachable poly(ethylene glycol) conjugates: cysteine-cleavable lipopolymers regenerating natural phospholipid, diacyl phosphatidylethanolamine. Bioconjug. Chem. 10(5), 703–707 (1999).
  • Song S, Liu D, Peng J et al. Novel peptide ligand directs liposomes toward EGF-R high-expressing cancer cells in vitro and in vivo. FASEB J. 23(5), 1396–1404 (2009).
  • Akinc A, Querbes W, De S et al. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol. Ther. 18(7), 1357–1364 (2010).
  • Andreu A, Fairweather N, Miller AD. Clostridium neurotoxin fragments as potential targeting moieties for liposomal gene delivery to the CNS. ChemBioChem 9(2), 219–231 (2008).
  • Waterhouse JE, Harbottle RP, Keller M et al. Synthesis and Application of Integrin Targeting Lipopeptides in Targeted Gene Delivery. ChemBioChem 6(7), 1212–1223 (2005).
  • Cardoso AL, Simoes S, de Almeida LP et al. Tf-lipoplexes for neuronal siRNA delivery: a promising system to mediate gene silencing in the CNS. J. Control. Rel. 132(2), 113–123 (2008).
  • Tietze N, Pelisek J, Philipp A et al. Induction of apoptosis in murine neuroblastoma by systemic delivery of transferrin-shielded siRNA polyplexes for downregulation of RNA. Oligonucleotides 18(2), 161–174 (2008).
  • Harbottle RP, Cooper RG, Hart SL et al. An RGD-oligolysine peptide: a prototype construct for integrin-mediated gene delivery. Human Gene. Ther. 9(7), 1037–1047 (1998).
  • Temming K, Schiffelers RM, Molema G, Kok RJ. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist. Updat. 8(6), 381–402 (2005).
  • Chu T, Ebright J, Ellington AD. Using aptamers to identify and enter cells. Curr. Opin. Mol. Ther. 9(2), 137–144 (2007).
  • Chu TC, Twu KY, Ellington AD, Levy M. Aptamer mediated siRNA delivery. Nucleic Acids Res. 34(10), e73 (2006).
  • 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(Web Server issue), W124–W129 (2004).
  • Naito Y, Yoshimura J, Morishita S, Ui-Tei K. siDirect 2.0: updated software for designing functional siRNA with reduced seed-dependent off-target effect. BMC Bioinformatics 10, 392 (2009).
  • 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 (2007).
  • 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(Web Server issue), W589–W591 (2005).
  • Judge AD, Sood V, Shaw JR, Fang D, McClintock K, MacLachlan I. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat. Biotechnol. 23(4), 457–462 (2005).
  • Olejniczak M, Galka-Marciniak P, Polak K, Fligier A, Krzyzosiak WJ. RNAimmuno: a database of the nonspecific immunological effects of RNA interference and microRNA reagents. RNA 18(5), 930–935 (2012).
  • Amarzguioui M, Rossi JJ, Kim D. Approaches for chemically synthesized siRNA and vector-mediated RNAi. FEBS Lett. 579(26), 5974–5981 (2005).
  • Zhou J, Neff CP, Liu X et al. Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice. Mol. Ther. 19(12), 2228–2238 (2011).
  • Ui-Tei K, Naito Y, Zenno S et al. 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(7), 2136–2151 (2008).
  • Watts JK, Deleavey GF, Damha MJ. Chemically modified siRNA: tools and applications. Drug Discov. Today 13(19-20), 842–855 (2008).
  • Stenvang J, Lindow M, Kauppinen S. Targeting of microRNAs for therapeutics. Biochem. Soc. Trans. 36(Pt 6), 1197–1200 (2008).
  • Frieden M, Orum H. The application of locked nucleic acids in the treatment of cancer. IDrugs 9(10), 706–711 (2006).
  • Fluiter K, Mook OR, Baas F. The therapeutic potential of LNA-modified siRNAs: reduction of off-target effects by chemical modification of the siRNA sequence. Methods Mol. Biol. 487, 189–203 (2009).
  • Judge AD, Bola G, Lee AC, MacLachlan I. Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol. Ther. 13(3), 494–505 (2006).
  • Judge A, MacLachlan I. Overcoming the innate immune response to small interfering RNA. Hum. Gene. Ther. 19(2), 111–124 (2008).
  • Robbins M, Judge A, Liang L, McClintock K, Yaworski E, MacLachlan I. 2'-O-methyl-modified RNAs act as TLR7 antagonists. Mol. Ther. 15(9), 1663–1669 (2007).
  • Robbins M, Judge A, MacLachlan I. siRNA and innate immunity. Oligonucleotides 19(2), 89–102 (2009).
  • Sioud M. Deciphering the code of innate immunity recognition of siRNAs. Methods Mol. Biol. 487, 41–59 (2009).
  • Bartlett DW, Davis ME. Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging. Nucleic Acids Res, 34(1), 322–333 (2006).
  • Eckstein F. Small non-coding RNAs as magic bullets. Trends. Biochem. Sci. 30(8), 445–452 (2005).
  • Overhoff M, Sczakiel G. Phosphorothioate-stimulated uptake of short interfering RNA by human cells. EMBO Rep. 6(12), 1176–1181 (2005).
  • Gao S, Dagnaes-Hansen F, Nielsen EJ et al. The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol. Ther. 17(7), 1225–1233 (2009).
  • Glud SZ, Bramsen JB, Dagnaes-Hansen F et al. Naked siLNA-mediated gene silencing of lung bronchoepithelium EGFP expression after intravenous administration. Oligonucleotides 19(2), 163–168 (2009).
  • Elmen J, Lindow M, Schutz S et al. LNA-mediated microRNA silencing in non-human primates. Nature 452(7189), 896–899 (2008).
  • Obad S, dos Santos CO, Petri A et al. Silencing of microRNA families by seed-targeting tiny LNAs. Nat. Gene. 43(4), 371–378 (2011).
  • Straarup EM, Fisker N, Hedtjarn M et al. Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates. Nucleic Acids Res. 38(20), 7100–7111 (2010).
  • Oliver M, Ahmad A, Kamaly N et al. MAGfect: a novel liposome formulation for MRI labelling and visualization of cells. Org. Biomol. Chem. 4(18), 3489–3497 (2006).
  • Miller AD. Lipid-based nanoparticles in cancer diagnosis and therapy. J. Drug Deliv. 165981 (2013).
  • Birchall J. Pulmonary delivery of nucleic acids. Expert Opin. Drug Deliv. 4(6), 575–578 (2007).
  • Thomas M, Lu JJ, Chen J, Klibanov AM. Non-viral siRNA delivery to the lung. Adv. Drug Deliv. Rev. 59(2-3), 124–133 (2007).
  • Boado RJ. Blood-brain barrier transport of non-viral gene and RNAi therapeutics. Pharm. Res. 24(9), 1772–1787 (2007).
  • Svensson RU, Shey MR, Ballas ZK et al. Assessing siRNA pharmacodynamics in a luciferase-expressing mouse. Mol. Ther. 16(12), 1995–2001 (2008).
  • Chen AA, Derfus AM, Khetani SR, Bhatia SN. Quantum dots to monitor RNAi delivery and improve gene silencing. Nucleic Acids Res. 33(22), e190 (2005).
  • Bonoiu A, Mahajan SD, Ye L et al. MMP-9 gene silencing by a quantum dot-siRNA nanoplex delivery to maintain the integrity of the blood brain barrier. Brain Res. 1282, 142–155 (2009).
  • Walther C, Meyer K, Rennert R, Neundorf I. Quantum dot-carrier peptide conjugates suitable for imaging and delivery applications. Bioconjug. Chem. 19(12), 2346–2356 (2008).
  • Johnson LN, Cashman SM, Kumar-Singh R. Cell-penetrating peptide for enhanced delivery of nucleic acids and drugs to ocular tissues including retina and cornea. Mol. Ther. 16(1), 107–114 (2008).
  • Bartlett DW, Su H, Hildebrandt IJ, Weber WA, Davis ME. 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(39), 15549–15554 (2007).
  • Medarova Z, Pham W, Farrar C, Petkova V, Moore A. In vivo imaging of siRNA delivery and silencing in tumors. Nat. Med. 13(3), 372–377 (2007).
  • Mikhaylova M, Stasinopoulos I, Kato Y, Artemov D, Bhujwalla ZM. Imaging of cationic multifunctional liposome-mediated delivery of COX-2 siRNA. Cancer Gene. Ther. 16(3), 217–226 (2009).
  • Yezhelyev MV, Qi L, O'Regan RM, Nie S, Gao X. Proton-sponge coated quantum dots for siRNA delivery and intracellular imaging. J. Am. Chem. Soc. 130(28), 9006–9012 (2008).
  • Laufer SD, Restle T. Peptide-mediated cellular delivery of oligonucleotide-based therapeutics in vitro: quantitative evaluation of overall efficacy employing easy to handle reporter systems. Curr. Pharm. Des. 14(34), 3637–3655 (2008).
  • Mescalchin A, Detzer A, Wecke M, Overhoff M, Wunsche W, Sczakiel G. Cellular uptake and intracellular release are major obstacles to the therapeutic application of siRNA: novel options by phosphorothioate-stimulated delivery. Expert Opin. Biol. Ther. 7(10), 1531–1538 (2007).
  • Detzer A, Overhoff M, Mescalchin A, Rompf M, Sczakiel G. Phosphorothioate-stimulated cellular uptake of siRNA: a cell culture model for mechanistic studies. Curr. Pharm. Des. 14(34), 3666–3673 (2008).
  • Detzer A, Overhoff M, Wunsche W et al. Increased RNAi is related to intracellular release of siRNA via a covalently attached signal peptide. RNA 15(4), 627–636 (2009).
  • Detzer A, Sczakiel G. Phosphorothioate-stimulated uptake of siRNA by mammalian cells: a novel route for delivery. Curr. Top Med. Chem. 9(12), 1109–1116 (2009).
  • White PJ. Barriers to successful delivery of short interfering RNA after systemic administration. Clin. Exp. Pharmacol. Physiol. 35(11), 1371–1376 (2008).
  • Wolff JA, Rozema DB. Breaking the bonds: non-viral vectors become chemically dynamic. Mol. Ther. 16(1), 8–15 (2008).
  • Lundberg P, El-Andaloussi S, Sutlu T, Johansson H, Langel U. Delivery of short interfering RNA using endosomolytic cell-penetrating peptides. FASEB J. 21(11), 2664–2671 (2007).
  • Heyes J, Palmer L, Bremner K, MacLachlan I. Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids. J. Control Rel. 107(2), 276–287 (2005).
  • Lavigne C, Thierry AR. Specific subcellular localization of siRNAs delivered by lipoplex in MCF-7 breast cancer cells. Biochimie 89(10), 1245–1251 (2007).
  • Buyens K, Meyer M, Wagner E, Demeester J, De Smedt SC, Sanders NN. Monitoring the disassembly of siRNA polyplexes in serum is crucial for predicting their biological efficacy. J. Control. Rel. 141(1), 38–41 (2010).
  • Kraljevic S, Pavelic K. Navigare necessere est. Improved navigation would help to solve two crucial problems in modern drug therapy: toxicity and precise delivery. EMBO Rep. 6(8), 695–700 (2005).
  • Omidi Y, Barar J, Akhtar S. Toxicogenomics of cationic lipid-based vectors for gene therapy: impact of microarray technology. Curr. Drug Deliv. 2(4), 429–441 (2005).
  • Bonnet ME, Erbacher P, Bolcato-Bellemin AL. Systemic delivery of DNA or siRNA mediated by linear polyethylenimine (L-PEI) does not induce an inflammatory response. Pharm. Res. 25(12), 2972–2982 (2008).
  • MacLachlan I, Judge A. Glucocorticoid modulation of nucleic acid-mediated immune stimulation. Protiva Biotherapeutics Inc., USA (2007).
  • Bumcrot D. Compositions and methods for inhibiting expression of Egs and VEGF genes. Alnylam Pharmaceuticals INC, USA (2009)
  • Leuschner PJ, Ameres SL, Kueng S, Martinez J. Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep. 7(3), 314–320 (2006).
  • Escriou V, Mignet N, Miller AD. Auto-associative lipid-based systems for nonviral nucleic acid delivery In: Advanced Textbook on Gene Transfer, Gene Therapy and Genetic Pharmacology. Scherman, D ( Ed.). Imperial College Press, London, UK (2013) ( In Press).
  • Miller AD, Tanner JA. The Essentials of Chemical Biology: Structure and Dynamics of Biological Macromolecules. J. Wiley, Chichester, UK (2008).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.