In vivo delivery of rnai with lipid-based nanoparticles

Annual Review of Biomedical Engineering

Volumn 13, Issue , 2011, Pages 507-530

  Huang, Leaf ^a   Liu, Yang ^a  

^a University of North Carolina   (United States)

Author keywords

Cationic lipid; Gene therapy; RNA interference; SiRNA

Indexed keywords

CATIONIC LIPIDS; CLINICAL TRIAL; DELIVERY SYSTEMS; HUMAN DISEASE; HUMAN THERAPEUTICS; IN-VIVO; RATIONAL DESIGN; RNA INTERFERENCE; SAFETY CONCERNS; SIRNA;

GENE THERAPY; GENETIC ENGINEERING; RNA; SAFETY ENGINEERING;

NANOPARTICLES;

ALN TTRO1; ALN VSP02; APOLIPOPROTEIN B; CYCLODEXTRIN; PROTEIN; SHORT HAIRPIN RNA; SMALL INTERFERING RNA; SOLID LIPID NANOPARTICLE; TRANSFERRIN; UNCLASSIFIED DRUG;

AMYLOIDOSIS; ARTICLE; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; ENDOSOME; GENE DELIVERY SYSTEM; GENE SILENCING; HUMAN; IN VIVO GENE TRANSFER; LIVER CANCER; LIVER CELL CARCINOMA; NONHUMAN; PATIENT SAFETY; PROTEIN DEFICIENCY; PROTEIN LOCALIZATION; RNA INTERFERENCE; RNA STABILITY;

ALGORITHMS; DRUG CARRIERS; GENE THERAPY; GENETIC DISEASES, INBORN; GENETIC VECTORS; HUMANS; LIPOSOMES; NANOPARTICLES; NEOPLASMS; PHARMACOKINETICS; POLYETHYLENE GLYCOLS; RNA INTERFERENCE; RNA, SMALL INTERFERING; VIRUS DISEASES;

EID: 79960530841     PISSN: 15239829     EISSN: 15454274     Source Type: Book Series    
DOI: 10.1146/annurev-bioeng-071910-124709     Document Type: Article

References (115)

1. Bernstein E, Caudy AA, Hammond SM, Hannon GJ. 2001. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363-66 (Pubitemid 32151243)
2. MeisterG, Tuschl T. 2004. Mechanisms of gene silencing by double-stranded RNA. Nature 431:343-49 (Pubitemid 39265674)
3. Bertrand JR, Pottier M, Vekris A, Opolon P, Maksimenko A, Malvy C. 2002. Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo. Biochem. Biophys. Res. Commun. 296:1000-4
4. KimDH, Rossi JJ. 2007. Strategies for silencing human disease using RNA interference. Nat. Rev. Genet. 8:173-84
5. Lee Y, Ahn C, Han J, Choi H, Kim J, et al. 2003. The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415-19 (Pubitemid 37187272)
6. Preall JB, Sontheimer EJ. 2005. RNAi: RISC gets loaded. Cell 123:543-45 (Pubitemid 41608456)
7. McCaffrey AP, Meuse L, Pham TT, Conklin DS, Hannon GJ, Kay MA. 2002. RNA interference in adult mice. Nature 418:38-39 (Pubitemid 34742563)
8. Morrissey DV, Lockridge JA, Shaw L, Blanchard K, Jensen K, et al. 2005. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat. Biotechnol. 23:1002-7 (Pubitemid 41114035)
9. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, et al. 2001. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106:23-34 (Pubitemid 32709955)
10. de Fougerolles A, VornlocherHP, Maraganore J, Lieberman J. 2007. Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug Discov. 6:443-53 (Pubitemid 47064567)
11. Lee Y, Jeon K, Lee JT, Kim S, Kim VN. 2002. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 21:4663-70
12. Taulli R, Bersani F, Foglizzo V, Linari A, Vigna E, et al. 2009. The muscle-specific microRNA miR-206 blocks human rhabdomyosarcoma growth in xenotransplanted mice by promoting myogenic differentiation. J. Clin. Investig. 119:2366-78
13. Baker M. 2010. RNA interference: homing in on delivery. Nature 464:1225-28
14. Chen Y, Zhu X, Zhang X, Liu B, Huang L. 2010. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol. Ther. 18:1650-56
15. Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, et al. 2009. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137:1005-17
16. van deWater FM,Boerman OC,Wouterse AC, Peters JG, Russel FG, MasereeuwR. 2006. Intravenously administered short interfering RNA accumulates in the kidney and selectively suppresses gene function in renal proximal tubules. Drug Metab. Dispos. 34:1393-97
17. Wolff JA, Rozema DB. 2008. Breaking the bonds: non-viral vectors become chemically dynamic. Mol. Ther. 16:8-15
18. Bragonzi A, Dina G, Villa A, Calori G, Biffi A, et al. 2000. Biodistribution and transgene expression with nonviral cationic vector/DNA complexes in the lungs. Gene Ther. 7:1753-60
19. Ishiwata H, Suzuki N, Ando S, Kikuchi H, Kitagawa T. 2000. Characteristics and biodistribution of cationic liposomes and their DNA complexes. J. Control. Release 69:139-48
20. Ishida O,Maruyama K, Sasaki K, IwatsuruM. 1999. Size-dependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice. Int. J. Pharm. 190:49-56 (Pubitemid 29467471)
21. Whitehead KA, Langer R, Anderson DG. 2009. Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 8:129-38
22. Di Guglielmo GM, Le Roy C, Goodfellow AF, Wrana JL. 2003. Distinct endocytic pathways regulate TGF-βreceptor signalling and turnover. Nat. Cell Biol. 5:410-21 (Pubitemid 36592263)
23. Bartlett DW,Davis ME. 2006. Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging. Nucleic Acids Res. 34:322-33 (Pubitemid 43160055)
24. BrummelkampTR, Bernards R, Agami R. 2002. A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550-53 (Pubitemid 34408678)
25. Paddison PJ, Caudy AA, Bernstein E, Hannon GJ, Conklin DS. 2002. Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev. 16:948-58 (Pubitemid 34408544)
26. Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, et al. 2006. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441:537-41 (Pubitemid 44050158)
27. Silva JM, Li MZ,Chang K,GeW,GoldingMC, et al. 2005. Second-generation shRNAlibraries covering the mouse and human genomes. Nat. Genet. 37:1281-88
28. McBride JL, Boudreau RL, Harper SQ, Staber PD, Monteys AM, et al. 2008. Artificial miRNAsmitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi. Proc. Natl. Acad. Sci. USA 105:5868-73
29. Rao DD, Vorhies JS, Senzer N, Nemunaitis J. 2009. siRNA versus shRNA: similarities and differences. Adv. Drug Deliv. Rev. 61:746-59
30. Vorhies JS, Nemunaitis JJ. 2009. Synthetic versus natural/biodegradable polymers for delivery of shRNAbased cancer therapies. Methods Mol. Biol. 480:11-29
31. Lam AP, Dean DA. 2010. Progress and prospects: nuclear import of nonviral vectors. Gene Ther. 17:439-47
32. Choung S, Kim YJ, Kim S, Park HO, Choi YC. 2006. Chemical modification of siRNAs to improve serum stability without loss of efficacy. Biochem. Biophys. Res. Commun. 342:919-27 (Pubitemid 43320485)
33. Braasch DA, Paroo Z, Constantinescu A, Ren G, Oz OK, et al. 2004. Biodistribution of phosphodiester and phosphorothioate siRNA. Bioorg. Med. Chem. Lett. 14:1139-43
34. Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, et al. 1987. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc. Natl. Acad. Sci. USA 84:7413-17
35. Owens DE 3rd, Peppas NA. 2006. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 307:93-102 (Pubitemid 41773257)
36. Frank MM, Fries LF. 1991. The role of complement in inflammation and phagocytosis. Immunol. Today 12:322-26
37. Mori A Klibanov AL,Torchilin VP,Huang L. 1991. Influence of the steric barrier activity of amphipathic poly(ethyleneglycol) and gangliosideGM1on the circulation time of liposomes and on the target binding of immunoliposomes in vivo. FEBS Lett. 284:263-66
38. Woodle MC, Matthay KK, Newman MS, Hidayat JE, Collins LR, et al. 1992. Versatility in lipid compositions showing prolonged circulation with sterically stabilized liposomes. Biochim. Biophys. Acta 1105:193-200
39. Roser M, Fischer D, Kissel T. 1998. Surface-modified biodegradable albumin nano-and microspheres. II: Effect of surface charges on in vitro phagocytosis and biodistribution in rats. Eur. J. Pharm. Biopharm. 46:255-63 (Pubitemid 29057671)
40. Matsumura Y, Maeda H. 1986. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46:6387-92
41. Hobbs SK,MonskyWL, Yuan F, RobertsWG, Griffith L, et al. 1998. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc. Natl. Acad. Sci. USA 95:4607-12
42. Jain RK. 1996. Delivery of molecular medicine to solid tumors. Science 271:1079-80
43. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, et al. 2009. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mousemodel of pancreatic cancer. Science 324:1457-61
44. Tokatlian T, Segura T. 2010. siRNA applications in nanomedicine. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2:305-15
45. 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. USA 104:15549-54 (Pubitemid 47502954)
46. Kirpotin DB, Drummond DC, Shao Y, Shalaby MR, Hong K, et al. 2006. Antibody targeting of longcirculating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res. 66:6732-40
47. Li SD,Huang L. 2010. Stealth nanoparticles: high density but sheddablePEGis a key for tumor targeting. J. Control. Release 145:178-81
48. Akinc A, Querbes W, De S, Qin J, Frank-Kamenetsky M, et al. 2010. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol. Ther. 18:1357-64
49. Marsh D, Bartucci R, Sportelli L. 2003. Lipid membranes with grafted polymers: physicochemical aspects. Biochim. Biophys. Acta 1615:33-59 (Pubitemid 37013466)
50. KenworthyAK, HristovaK,NeedhamD,McIntoshTJ. 1995. Range and magnitude of the steric pressure between bilayers containing phospholipids with covalently attached poly(ethylene glycol). Biophys. J. 68:1921-36
51. Moghimi SM, Szebeni J. 2003. Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog. Lipid Res. 42:463-78 (Pubitemid 37237636)
52. Bedu-Addo FK, Tang P, Xu Y, Huang L. 1996. Effects of polyethyleneglycol chain length and phospholipid acyl chain composition on the interaction of polyethyleneglycol-phospholipid conjugates with phospholipid: implications in liposomal drug delivery. Pharm. Res. 13:710-17
53. Shimada K, Matsuo S, Sadzuka Y,Miyagishima A, Nozawa Y, et al. 2000. Determination of incorporated amounts of poly(ethylene glycol)-derivatized lipids in liposomes for the physicochemical characterization of stealth liposomes. Int. J. Pharm. 203:255-63 (Pubitemid 30627645)
54. Kingshott P, Thissen H, Griesser HJ. 2002. Effects of cloud-point grafting, chain length, and density of PEG layers on competitive adsorption of ocular proteins. Biomaterials 23:2043-56
55. Li SD, Huang L. 2009. Nanoparticles evading the reticuloendothelial system: role of the supported bilayer. Biochim. Biophys. Acta 1788:2259-66
56. Li SD, Huang L. 2008. Pharmacokinetics and biodistribution of nanoparticles. Mol. Pharm. 5:496-504
57. Li SD, Chono S, Huang L. 2008. Efficient oncogene silencing and metastasis inhibition via systemic delivery of siRNA. Mol. Ther. 16:942-46 (Pubitemid 351587105)
58. Parr MJ, Masin D, Cullis PR, Bally MB. 1997. Accumulation of liposomal lipid and encapsulated doxorubicin in murine Lewis lung carcinoma: the lack of beneficial effects by coating liposomes with poly(ethylene glycol). J. Pharmacol. Exp. Ther. 280:1319-27
59. Hong RL, Huang CJ, Tseng YL, Pang VF, Chen ST, et al. 1999. Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice: is surface coating with polyethylene glycol beneficial? Clin. Cancer Res. 5:3645-52
60. Semple SC, Harasym TO, Clow KA, Ansell SM, Klimuk SK, Hope MJ. 2005. Immunogenicity and rapid blood clearance of liposomes containing polyethylene glycol-lipid conjugates and nucleic acid. J. Pharmacol. Exp. Ther. 312:1020-26
61. Ishida T, Wang X, Shimizu T, Nawata K, Kiwada H. 2007. PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. J. Control. Release 122:349-55 (Pubitemid 47407760)
62. Judge A, McClintock K, Phelps JR,Maclachlan I. 2006. Hypersensitivity and loss of disease site targeting caused by antibody responses to PEGylated liposomes. Mol. Ther. 13:328-37 (Pubitemid 43056898)
63. Tagami T, Nakamura K, Shimizu T, Ishida T, KiwadaH. 2009. Effect of siRNA in PEG-coated siRNAlipoplex on anti-PEG IgM production. J. Control. Release 137:234-40
64. Tagami T, Nakamura K, Shimizu T, Yamazaki N, Ishida T, Kiwada H. 2010. CpG motifs in pDNAsequences increase anti-PEG IgM production induced by PEG-coated pDNA-lipoplexes. J. Control. Release 142:160-66
65. Holland JW, Hui C, Cullis PR, Madden TD. 1996. Poly(ethylene glycol)-lipid conjugates regulate the calcium-induced fusion of liposomes composed of phosphatidylethanolamine and phosphatidylserine. Biochemistry 35:2618-24
66. Wheeler JJ, Palmer L, Ossanlou M, MacLachlan I, Graham RW, et al. 1999. Stabilized plasmid-lipid particles: construction and characterization. Gene Ther. 6:271-81 (Pubitemid 29089926)
67. Fenske DB, MacLachlan I, Cullis PR. 2002. Stabilized plasmid-lipid particles: a systemic gene therapy vector. Methods Enzymol. 346:36-71 (Pubitemid 41103130)
68. Monck MA, Mori A, Lee D, Tam P, Wheeler JJ, et al. 2000. Stabilized plasmid-lipid particles: pharmacokinetics and plasmid delivery to distal tumors following intravenous injection. J. Drug Target 7:439-52 (Pubitemid 30184580)
69. Mandel R, Ryser HJ, Niaki B, Ghani F, ShenWC. 1991. Isolation of variants of Chinese hamster ovary cells with abnormally low levels of GSH: decreased ability to cleave endocytosed disulfide bonds. J. Cell. Physiol. 149:60-65 (Pubitemid 21910166)
70. Short S, Merkel BJ, Caffrey R, McCoy KL. 1996. Defective antigen processing correlates with a low level of intracellular glutathione. Eur. J. Immunol. 26:3015-20
71. GuoX, SzokaFCJr. 2001. Steric stabilization of fusogenic liposomes by a low-pH sensitive PEG-diortho ester-lipid conjugate. Bioconjug. Chem. 12:291-300 (Pubitemid 32235482)
72. Walker GF, Fella C, Pelisek J, Fahrmeir J, Boeckle S, et al. 2005. Toward synthetic viruses: endosomal pH-triggered deshielding of targeted polyplexes greatly enhances gene transfer in vitro and in vivo. Mol. Ther. 11:418-25 (Pubitemid 40277318)
73. Zhang JX, Zalipsky S, Mullah N, Pechar M, Allen TM. 2004. Pharmaco attributes of dioleoylphosphatidylethanolamine/cholesterylhemisuccinate liposomes containing different types of cleavable lipopolymers. Pharmacol. Res. 49:185-98 (Pubitemid 37485715)
74. Zalipsky S, Qazen M, Walker JA 2nd, Mullah N, Quinn YP, Huang SK. 1999. New detachable poly(ethylene glycol) conjugates: cysteine-cleavable lipopolymers regenerating natural phospholipid, diacyl phosphatidylethanolamine. Bioconjug. Chem. 10:703-7 (Pubitemid 29456355)
75. Hatakeyama H, Akita H, Kogure K, Oishi M, Nagasaki Y, et al. 2007. Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid. Gene Ther. 14:68-77 (Pubitemid 44942867)
76. Turner JJ, Jones SW, Moschos SA, Lindsay MA, Gait MJ. 2007. MALDI-TOF mass spectral analysis of siRNA degradation in serum confirms an RNAse A-like activity. Mol. Biosyst. (1):43-50 (Pubitemid 44924958)
77. Boussif O, Lezoualc'h F, Zanta MA, Mergny MD, Scherman D, et al. 1995. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc. Natl. Acad. Sci. USA 92:7297-301
78. Thomas M, Klibanov AM. 2002. Enhancing polyethylenimine's delivery of plasmid DNA into mammalian cells. Proc. Natl. Acad. Sci. USA 99:14640-45 (Pubitemid 35334537)
79. Sonawane ND, Szoka FC Jr, Verkman AS. 2003. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. J. Biol. Chem. 278:44826-31 (Pubitemid 37377241)
80. Akinc A, ThomasM, Klibanov AM, Langer R. 2005. Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis. J. Gene Med. 7:657-63 (Pubitemid 40744532)
81. Xu Y, Szoka FC Jr. 1996. Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry 35:5616-23
82. Hafez IM, Maurer N, Cullis PR. 2001. On the mechanism whereby cationic lipids promote intracellular delivery of polynucleic acids. Gene Ther. 8:1188-96
83. Gruner SM, Cullis PR, Hope MJ, Tilcock CPS. 1985. Lipid polymorphism: the molecular basis of nonbilayer phases. Annu. Rev. Biophys. Biophys. Chem. 14:211-38
84. Madden TD, Cullis PR. 1982. Stabilization of bilayer structure for unsaturated phosphatidylethanolamines by detergents. Biochim. Biophys. Acta 684:149-53
85. Holland JW, Cullis PR, Madden TD. 1996. Poly(ethylene glycol)-lipid conjugates promote bilayer formation in mixtures of non-bilayer-forming lipids. Biochemistry 35:2610-17
86. Hafez IM, Cullis PR. 2001. Roles of lipid polymorphism in intracellular delivery. Adv. Drug Deliv. Rev. 47:139-48 (Pubitemid 32324111)
87. Tseng YC, Mozumdar S, Huang L. 2009. Lipid-based systemic delivery of siRNA. Adv. Drug Deliv. Rev. 61:721-31
88. Li J, Chen YC, Tseng YC,Mozumdar S,Huang L. 2010. Biodegradable calcium phosphate nanoparticle with lipid coating for systemic siRNA delivery. J. Control. Release 142:416-21
89. Lu JJ, Langer R, Chen J. 2009. A novel mechanism is involved in cationic lipid-mediated functional siRNA delivery. Mol. Pharm. 6:763-71
90. Semple SC, Akinc A, Chen J, Sandhu AP, Mui BL, et al. 2010. Rational design of cationic lipids for siRNA delivery. Nat. Biotechnol. 28:172-76
91. Akinc A, Zumbuehl A, Goldberg M, Leshchiner ES, Busini V, et al. 2008. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat. Biotechnol. 26:561-69 (Pubitemid 351668042)
92. Love KT, Mahon KP, Levins CG, Whitehead KA, Querbes W, et al. 2010. Lipid-like materials for low-dose, in vivo gene silencing. Proc. Natl. Acad. Sci. USA 107:1864-69
93. Frank-Kamenetsky M, Grefhorst A, Anderson NN, Racie TS, Bramlage B, et al. 2008. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc. Natl. Acad. Sci. USA 105:11915-20
94. Birmingham A, Anderson EM, Reynolds A, Ilsley-Tyree D, Leake D, et al. 2006. 3UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods 3:199-204
95. Jackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, et al. 2003. Expression profiling reveals off-target gene regulation by RNAi. Nat. Biotechnol. 21:635-37 (Pubitemid 36638089)
96. Jackson AL, Burchard J, Leake D, Reynolds A, Schelter J, et al. 2006. Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA 12:1197-205 (Pubitemid 43990545)
97. Decherf S, Hassani Z, Demeneix BA. 2008. In vivo siRNA delivery to the mouse hypothalamus shows a role of the co-chaperone XAP2 in regulating TRH transcription. Methods Mol. Biol. 433:355-66
98. Sledz CA, HolkoM, de Veer MJ, Silverman RH, Williams BR. 2003. Activation of the interferon system by short-interfering RNAs. Nat. Cell Biol. 5:834-39 (Pubitemid 37087172)
99. Kariko K, Bhuyan P, Capodici J, Weissman D. 2004. Small interfering RNAs mediate sequenceindependent gene suppression and induce immune activation by signaling through Toll-like receptor 3. J. Immunol. 172:6545-49
100. Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, et al. 2005. Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med. 11:263-70 (Pubitemid 40460553)
101. Judge AD, Sood V, Shaw JR, Fang D, McClintock K, MacLachlan I. 2005. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat. Biotechnol. 23:457-62 (Pubitemid 41724921)
102. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, et al. 2004. Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303:1526-29
103. Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C. 2004. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529-31
104. Robbins M, Judge A, Ambegia E, Choi C, Yaworski E, et al. 2008. Misinterpreting the therapeutic effects of small interfering RNA caused by immune stimulation. Hum. Gene Ther. 19:991-99
105. Lonez C, Vandenbranden M, Ruysschaert JM. 2008. Cationic liposomal lipids: from gene carriers to cell signaling. Prog. Lipid Res. 47:340-47
106. Latif N, Bachhawat BK. 1984. The effect of surface charges of liposomes in immunopotentiation. Biosci. Rep. 4:99-107
107. Perrie Y, Frederik PM, Gregoriadis G. 2001. Liposome-mediated DNA vaccination: the effect of vesicle composition. Vaccine 19:3301-10
108. Vangasseri DP,Cui Z, ChenW,Hokey DA, FaloLDJr,Huang L. 2006. Immunostimulation of dendritic cells by cationic liposomes. Mol. Membr. Biol. 23:385-95 (Pubitemid 44630022)
109. Cui Z, Han SJ, Vangasseri DP, Huang L. 2005. Immunostimulation mechanism of LPD nanoparticle as a vaccine carrier. Mol. Pharm. 2:22-28 (Pubitemid 40314726)
110. YanW, ChenW,Huang L. 2007. Mechanism of adjuvant activity of cationic liposome: phosphorylation of a MAP kinase, ERK and induction of chemokines. Mol. Immunol. 44:3672-81
111. Vangasseri DP, Han SJ, Huang L. 2005. Lipid-protamine-DNA-mediated antigen delivery. Curr. Drug Deliv. 2:401-6 (Pubitemid 41277772)
112. Omidi Y, Hollins AJ, Benboubetra M, Drayton R, Benter IF, Akhtar S. 2003. Toxicogenomics of nonviral vectors for gene therapy: a microarray study of lipofectin-and oligofectamine-induced gene expression changes in human epithelial cells. J. Drug Target 11:311-23 (Pubitemid 38081335)
113. Hollins AJ, Omidi Y, Benter IF, Akhtar S. 2007. Toxicogenomics of drug delivery systems: exploiting delivery system-induced changes in target gene expression to enhance siRNA activity. J. Drug Target 15:83-88 (Pubitemid 47161335)
114. Vaishnaw AK, Gollob J, Gamba-Vitalo C, Hutabarat R, Sah D, et al. 2010. A status report on RNAi therapeutics. Silence 1:14
115. Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, et al. 2010. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464:1067-70