Cellular delivery of siRNA and antisense oligonucleotides via receptor-mediated endocytosis

Expert Opinion on Drug Delivery

Volumn 8, Issue 4, 2011, Pages 435-449

  Ming, Xin ^a  

^a University of North Carolina   (United States)

Author keywords

Antisense; cellular delivery; endocytosis; oligonucleotides; siRNA; targeted delivery; trafficking

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; APTAMER; ASIALOGLYCOPROTEIN RECEPTOR; BOMBESIN RECEPTOR; CELL PENETRATING PEPTIDE; CELL SURFACE RECEPTOR; CHOLESTEROL; CLATHRIN; EPIDERMAL GROWTH FACTOR RECEPTOR; GUANOSINE TRIPHOSPHATASE; IMMUNOLIPOSOME; INTEGRIN; LOCKED NUCLEIC ACID; NANOCARRIER; NANOPARTICLE; OLIGONUCLEOTIDE; PEPTIDE NUCLEIC ACID; PROSTATE SPECIFIC MEMBRANE ANTIGEN; PROTEIN P53; RNA INDUCED SILENCING COMPLEX; SMALL INTERFERING RNA; SOMATOMEDIN C RECEPTOR; SPLICE SWITCHING OLIGONUCLEOTIDE; TRANSFERRIN RECEPTOR; UNCLASSIFIED DRUG;

ACUTE KIDNEY FAILURE; ANTISENSE THERAPY; CAVEOLA; CELL TRANSPORT; CELLULAR DISTRIBUTION; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; DRUG TARGETING; DUCHENNE MUSCULAR DYSTROPHY; ENDOCYTOSIS; ENDOSOME; HUMAN; INTERNALIZATION; KUPFFER CELL; LYSOSOME; MACROPINOCYTOSIS; NONHUMAN; PHAGOCYTOSIS; PINOCYTOSIS; PROSTATE CANCER; PROTEIN TARGETING; RECEPTOR BINDING; REVIEW; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SOLID TUMOR; TRANS GOLGI NETWORK; TRANSCYTOSIS; VIRUS INHIBITION; VIRUS REPLICATION;

ANIMALS; DRUG DELIVERY SYSTEMS; ENDOCYTOSIS; ENDOSOMES; HUMANS; OLIGONUCLEOTIDES, ANTISENSE; PROTEIN BINDING; RECEPTORS, CELL SURFACE; RNA, SMALL INTERFERING;

EID: 79952937538     PISSN: 17425247     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425247.2011.561313     Document Type: Review

References (110)

1. Vaishnaw AK, Gollob J, Gamba-Vitalo C, et al. A status report on RNAi therapeutics. Silence 2010;1(1):14. A review including clinical trials of siRNAs.
2. Castanotto D, Rossi JJ. The promises and pitfalls of RNA-interference- based therapeutics. Nature 2009;457(7228):426-33
3. Bennett CF, Swayze EE. RNA targeting therapeutics: Molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol 2010;50:259-93. A review on pharmacology of antisense and siRNA oligonucleotides.
4. Bauman J, Jearawiriyapaisarn N, Kole R. Therapeutic potential of splice-switching oligonucleotides. Oligonucleotides 2009;19(1):1-13
5. Juliano R, Bauman J, Kang H, et al. Biological barriers to therapy with antisense and siRNA oligonucleotides. Mol Pharm 2009;6(3):686-95. A review on delivery barriers of antisense and siRNA oligonucleotides.
6. Whitehead KA, Langer R, Anderson DG. Knocking down barriers: Advances in siRNA delivery. Nat Rev Drug Discov 2009;8(2):129-38
7. Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature 2003;422(6927):37-44 (Pubitemid 36323287)
8. Damke H. Dynamin and receptor-mediated endocytosis. FEBS Lett 1996;389(1):48-51 (Pubitemid 26227424)
9. Sudhof TC, Rothman JE. Membrane fusion: Grappling with SNARE and SM proteins. Science 2009;323(5913):474-7
10. Stenmark H. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 2009;10(8):513-25
11. Dominska M, Dykxhoorn DM. Breaking down the barriers: SiRNA delivery and endosome escape. J Cell Sci 2010;123(Pt 8):1183-9
12. Kwon EJ, Bergen JM, Pun SH. Application of an HIV gp41-derived peptide for enhanced intracellular trafficking of synthetic gene and siRNA delivery vehicles. Bioconjug Chem 2008;19(4):920-7 (Pubitemid 351614546)
13. Detzer A, Overhoff M, Wunsche W, et al. Increased RNAi is related to intracellular release of siRNA via a covalently attached signal peptide. RNA 2009;15(4):627-36. A report on endosomal release in PS-stimulated siRNA delivery.
14. Fisher TL, Terhorst T, Cao X, et al. Intracellular disposition and metabolism of fluorescently-labeled unmodified and modified oligonucleotides microinjected into mammalian cells. Nucleic Acids Res 1993;21(16):3857-65 (Pubitemid 23254510)
15. Iversen PL, Zhu S, Meyer A, et al. Cellular uptake and subcellular distribution of phosphorothioate oligonucleotides into cultured cells. Antisense Res Dev 1992;2(3):211-22
16. Takakura Y, Mahato RI, Yoshida M, et al. Uptake characteristics of oligonucleotides in the isolated rat liver perfusion system. Antisense Nucleic Acid Drug Dev 1996;6(3):177-83 (Pubitemid 26394877)
17. Drin G, Mazel M, Clair P, et al. Physico-chemical requirements for cellular uptake of pAntp peptide. Role of lipid-binding affinity. Eur J Biochem 2001;268(5):1304-14 (Pubitemid 32231883)
18. Richard JP, Melikov K, Vives E, et al. Cell-penetrating peptides. A reevaluation of the mechanism of cellular uptake. J Biol Chem 2003;278(1):585-90 (Pubitemid 36043612)
19. de Diesbach P, N'Kuli F, Berens C, et al. Receptor-mediated endocytosis of phosphodiester oligonucleotides in the HepG2 cell line: Evidence for non-conventional intracellular trafficking. Nucleic Acids Res 2002;30(7):1512-21 (Pubitemid 34679726)
20. Beltinger C, Saragovi HU, Smith RM, et al. Binding, uptake, and intracellular trafficking of phosphorothioate-modified oligodeoxynucleotides. J Clin Invest 1995;95(4):1814-23
21. Geary RS. Antisense oligonucleotide pharmacokinetics and metabolism. Expert Opin Drug Metab Toxicol 2009;5(4):381-91
22. Bijsterbosch MK, Manoharan M, Rump ET, et al. In vivo fate of phosphorothioate antisense oligodeoxynucleotides: Predominant uptake by scavenger receptors on endothelial liver cells. Nucleic Acids Res 1997;25(16):3290-6 (Pubitemid 27338689)
23. Biessen EA, Vietsch H, Kuiper J, et al. Liver uptake of phosphodiester oligodeoxynucleotides is mediated by scavenger receptors. Mol Pharmacol 1998;53(2):262-9 (Pubitemid 28099736)
24. Sawai K, Mahato RI, Oka Y, et al. Disposition of oligonucleotides in isolated perfused rat kidney: Involvement of scavenger receptors in their renal uptake. J Pharmacol Exp Ther 1996;279(1):284-90 (Pubitemid 27166923)
25. Butler M, Crooke RM, Graham MJ, et al. Phosphorothioate oligodeoxynucleotides distribute similarly in class A scavenger receptor knockout and wild-type mice. J Pharmacol Exp Ther 2000;292(2):489-96 (Pubitemid 30067410)
26. Benimetskaya L, Loike JD, Khaled Z, et al. Mac-1 (CD11b/CD18) is an oligodeoxynucleotide-binding protein. Nat Med 1997;3(4):414-20 (Pubitemid 27145683)
27. Alam MR, Ming X, Dixit V, et al. The biological effect of an antisense oligonucleotide depends on its route of endocytosis and trafficking. Oligonucleotides 2010;20(2):103-9. A study on effects of trafficking pathway on pharmacology of antisense and oligonucleotides.
28. Stein CA, Hansen JB, Lai J, et al. Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents. Nucleic Acids Res 2010;38(1):e3
29. Eulalio A, Behm-Ansmant I, Izaurralde E. P bodies: At the crossroads of post-transcriptional pathways. Nat Rev Mol Cell Biol 2007;8(1):9-22 (Pubitemid 46012011)
30. Molitoris BA, Dagher PC, Sandoval RM, et al. siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury. J Am Soc Nephrol 2009;20(8):1754-64. A study on free siRNA uptake in renal tubular cells in rats.
31. Zheng X, Zhang X, Feng B, et al. Gene silencing of complement C5a receptor using siRNA for preventing ischemia/ reperfusion injury. Am J Pathol 2008;173(4):973-80
32. van de Water FM, Boerman OC, Wouterse AC, et al. Intravenously administered short interfering RNA accumulates in the kidney and selectively suppresses gene function in renal proximal tubules. Drug Metab Dispos 2006;34(8):1393-7 (Pubitemid 44079881)
33. Bitko V, Musiyenko A, Shulyayeva O, et al. Inhibition of respiratory viruses by nasally administered siRNA. Nat Med 2005;11(1):50-5 (Pubitemid 40215837)
34. Winston WM, Molodowitch C, Hunter CP. Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science 2002;295(5564):2456-9 (Pubitemid 34270260)
35. Duxbury MS, Ashley SW, Whang EE. RNA interference: A mammalian SID-1 homologue enhances siRNA uptake and gene silencing efficacy in human cells. Biochem Biophys Res Commun 2005;331(2):459-63 (Pubitemid 40602659)
36. Wolfrum C, Shi S, Jayaprakash KN, et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat Biotechnol 2007;25(10):1149-57 (Pubitemid 47538115)
37. Overhoff M, Sczakiel G. Phosphorothioate-stimulated uptake of short interfering RNA by human cells. EMBO Rep 2005;6(12):1176-81 (Pubitemid 41741702)
38. Detzer A, Overhoff M, Mescalchin A, et al. Phosphorothioate-stimulated cellular uptake of siRNA: A cell culture model for mechanistic studies. Curr Pharm Des 2008;14(34):3666-73
39. Oliveira S, Hogset A, Storm G, et al. Delivery of siRNA to the target cell cytoplasm: Photochemical internalization facilitates endosomal escape and improves silencing efficiency, in vitro and in vivo. Curr Pharm Des 2008;14(34):3686-97
40. Astriab-Fisher A, Sergueev DS, Fisher M, et al. Antisense inhibition of P-glycoprotein expression using peptide-oligonucleotide conjugates. Biochem Pharmacol 2000;60(1):83-90 (Pubitemid 30243088)
41. Simeoni F, Morris MC, Heitz F, et al. Insight into the mechanism of the peptide-based gene delivery system MPG: Implications for delivery of siRNA into mammalian cells. Nucleic Acids Res 2003;31(11):2717-24 (Pubitemid 37442116)
42. Abes S, Moulton HM, Clair P, et al. Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents. J Control Release 2006;116(3):304-13 (Pubitemid 44827406)
43. Wu B, Moulton HM, Iversen PL, et al. Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer. Proc Natl Acad Sci USA 2008;105(39):14814-19
44. Yin H, Moulton HM, Betts C, et al. A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice. Hum Mol Genet 2009;18(22):4405-14
45. Crombez L, Morris MC, Dufort S, et al. Targeting cyclin B1 through peptide-based delivery of siRNA prevents tumour growth. Nucleic Acids Res 2009;37(14):4559-69
46. Eguchi A, Meade BR, Chang YC, et al. Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein. Nat Biotechnol 2009;27(6):567-71. A study on systemic siRNA delivery by means of CPP complexes.
47. Mok H, Park TG. Self-crosslinked and reducible fusogenic peptides for intracellular delivery of siRNA. Biopolymers 2008;89(10):881-8
48. Derossi D, Calvet S, Trembleau A, et al. Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. J Biol Chem 1996;271(30):18188-93 (Pubitemid 26250811)
49. Richard JP, Melikov K, Brooks H, et al. Cellular uptake of unconjugated TAT peptide involves clathrin-dependent endocytosis and heparan sulfate receptors. J Biol Chem 2005;280(15):15300-6 (Pubitemid 40562886)
50. Wadia JS, Stan RV, Dowdy SF. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat Med 2004;10(3):310-15 (Pubitemid 38667624)
51. Kaplan IM, Wadia JS, Dowdy SF. Cationic TAT peptide transduction domain enters cells by macropinocytosis. J Control Release 2005;102(1):247-53 (Pubitemid 40093789)
52. Fittipaldi A, Ferrari A, Zoppe M, et al. Cell membrane lipid rafts mediate caveolar endocytosis of HIV-1 Tat fusion proteins. J Biol Chem 2003;278(36):34141-9 (Pubitemid 37553255)
53. Ter-Avetisyan G, Tunnemann G, Nowak D, et al. Cell entry of arginine-rich peptides is independent of endocytosis. J Biol Chem 2009;284(6):3370-8
54. Chiu YL, Ali A, Chu CY, et al. Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells. Chem Biol 2004;11(8):1165-75 (Pubitemid 39138769)
55. Lorenz C, Hadwiger P, John M, et al. Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells. Bioorg Med Chem Lett 2004;14(19):4975-7 (Pubitemid 39165605)
56. Soutschek J, Akinc A, Bramlage B, et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 2004;432(7014):173-8. First study showing systemic delivery of siRNA conjugates causes knockdown. (Pubitemid 39545841)
57. Nishina K, Unno T, Uno Y, et al. Efficient in vivo delivery of siRNA to the liver by conjugation of alpha-tocopherol. Mol Ther 2008;16(4):734-40 (Pubitemid 351426175)
58. 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 2007;15(6):1145-52 (Pubitemid 46813617)
59. Sato Y, Murase K, Kato J, et al. Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat Biotechnol 2008;26(4):431-42 (Pubitemid 351501817)
60. Stockert RJ. The asialoglycoprotein receptor: Relationships between structure, function, and expression. Physiol Rev 1995;75(3):591-609
61. Biessen EA, Vietsch H, Rump ET, et al. Targeted delivery of oligodeoxynucleotides to parenchymal liver cells in vivo. Biochem J 1999;340(Pt 3):783-92 (Pubitemid 29312878)
62. Biessen EA, Sliedregt-Bol K, Pa TH, et al. Design of a targeted peptide nucleic acid prodrug to inhibit hepatic human microsomal triglyceride transfer protein expression in hepatocytes. Bioconjug Chem 2002;13(2):295-302 (Pubitemid 34267941)
63. Rozema DB, Lewis DL, Wakefield DH, et al. Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes. Proc Natl Acad Sci USA 2007;104(32):12982-7. A study using a multifunctional system to deliver siRNAs. (Pubitemid 351737577)
64. Zhu L, Mahato RI. Targeted delivery of siRNA to hepatocytes and hepatic stellate cells by bioconjugation. Bioconjug Chem 2010;21(11):2119-27
65. Sato A, Takagi M, Shimamoto A, et al. Small interfering RNA delivery to the liver by intravenous administration of galactosylated cationic liposomes in mice. Biomaterials 2007;28(7):1434-42 (Pubitemid 44959042)
66. Alam MR, Dixit V, Kang H, et al. Intracellular delivery of an anionic antisense oligonucleotide via receptor-mediated endocytosis. Nucleic Acids Res 2008;36(8):2764-76 (Pubitemid 351659588)
67. Kang H, Alam MR, Dixit V, et al. Cellular delivery and biological activity of antisense oligonucleotides conjugated to a targeted protein carrier. Bioconjug Chem 2008;19(11):2182-8
68. Schiffelers RM, Ansari A, Xu J, et al. Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Res 2004;32(19):e149
69. Wang 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(3):207-13
70. Ming X, Alam MR, Fisher M, et al. Intracellular delivery of an antisense oligonucleotide via endocytosis of a G protein-coupled receptor. Nucleic Acids Res 2010;38(19):6567-76
71. Basu S, Wickstrom E. Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insulin-like growth factor 1 for increased cellular uptake. Bioconjug Chem 1997;8(4):481-8 (Pubitemid 27347553)
72. Cesarone G, Edupuganti OP, Chen CP, et al. Insulin receptor substrate 1 knockdown in human MCF7 ER+ breast cancer cells by nuclease-resistant IRS1 siRNA conjugated to a disulfide-bridged D-peptide analogue of insulin-like growth factor 1. Bioconjug Chem 2007;18(6):1831-40 (Pubitemid 350219981)
73. Davis ME, Zuckerman JE, Choi CH, et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 2010;464(7291):1067-70. The first clinical trial to use targeted nanoparticles to deliver siRNA.
74. 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 Ran. Oligonucleotides 2008;18(2):161-74 (Pubitemid 352019749)
75. Shir A, Ogris M, Wagner E, et al. EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice. PLoS Med 2006;3(1):e6
76. Kumar P, Wu H, McBride JL, et al. Transvascular delivery of small interfering RNA to the central nervous system. Nature 2007;448(7149):39-43. The first study to use targeted complexes to deliver siRNA to brain. (Pubitemid 47037001)
77. Song E, Zhu P, Lee SK, et al. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol 2005;23(6):709-17. The first study to use antibody complexes to deliver siRNAs. (Pubitemid 41716361)
78. Peer D, Zhu P, Carman CV, et al. Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1. Proc Natl Acad Sci USA 2007;104(10):4095-100 (Pubitemid 47181584)
79. Kumar P, Ban HS, Kim SS, et al. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 2008;134(4):577-86
80. Peer D, Park EJ, Morishita Y, et al. Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science 2008;319(5863):627-30 (Pubitemid 351197066)
81. Pirollo KF, Zon G, Rait A, et al. Tumor-targeting nanoimmunoliposome complex for short interfering RNA delivery. Hum Gene Ther 2006;17(1):117-24 (Pubitemid 43100520)
82. Kim SS, Peer D, Kumar P, et al. RNAi-mediated CCR5 silencing by LFA-1-targeted nanoparticles prevents HIV infection in BLT mice. Mol Ther 2010;18(2):370-6
83. Keefe AD, Pai S, Ellington A. Aptamers as therapeutics. Nat Rev Drug Discov 2010;9(7):537-50
84. Chu TC, Twu KY, Ellington AD, et al. Aptamer mediated siRNA delivery. Nucleic Acids Res 2006;34(10):e73
85. McNamara JO II, Andrechek ER, Wang Y, et al. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 2006;24(8):1005-15 (Pubitemid 44215395)
86. Dassie JP, Liu XY, Thomas GS, et al. Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nat Biotechnol 2009;27(9):839-49
87. Zhou J, Swiderski P, Li H, et al. Selection, characterization and application of new RNA HIV gp 120 aptamers for facile delivery of Dicer substrate siRNAs into HIV infected cells. Nucleic Acids Res 2009;37(9):3094-109
88. Zhou J, Li H, Li S, et al. Novel dual inhibitory function aptamer-siRNA delivery system for HIV-1 therapy. Mol Ther 2008;16(8):1481-9
89. Kortylewski M, Swiderski P, Herrmann A, et al. In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nat Biotechnol 2009;27(10):925-32
90. Armbruster BN, Roth BL. Mining the receptorome. J Biol Chem 2005;280(7):5129-32 (Pubitemid 40279980)
91. Lagerstrom MC, Schioth HB. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat Rev Drug Discov 2008;7(4):339-57
92. Lundberg P, El-Andaloussi S, Sutlu T, et al. Delivery of short interfering RNA using endosomolytic cell-penetrating peptides. FASEB J 2007;21(11):2664-71 (Pubitemid 47372734)
93. Pichon C, Arar K, Stewart AJ, et al. Intracellular routing and inhibitory activity of oligonucleopeptides containing a KDEL motif. Mol Pharmacol 1997;51(3):431-8 (Pubitemid 27118479)
94. Aldrian-Herrada G, Desarmenien MG, Orcel H, et al. A peptide nucleic acid (PNA) is more rapidly internalized in cultured neurons when coupled to a retro-inverso delivery peptide. The antisense activity depresses the target mRNA and protein in magnocellular oxytocin neurons. Nucleic Acids Res 1998;26(21):4910-16 (Pubitemid 28491169)
95. Pooga M, Soomets U, Hallbrink M, et al. Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo. Nat Biotechnol 1998;16(9):857-61 (Pubitemid 28405857)
96. Astriab-Fisher A, Sergueev D, Fisher M, et al. Conjugates of antisense oligonucleotides with the Tat and antennapedia cell-penetrating peptides: Effects on cellular uptake, binding to target sequences, and biologic actions. Pharm Res 2002;19(6):744-54 (Pubitemid 34686732)
97. Turner JJ, Ivanova GD, Verbeure B, et al. Cell-penetrating peptide conjugates of peptide nucleic acids (PNA) as inhibitors of HIV-1 Tat-dependent trans-activation in cells. Nucleic Acids Res 2005;33(21):6837-49 (Pubitemid 43000315)
98. Davidson TJ, Harel S, Arboleda VA, et al. Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation. J Neurosci 2004;24(45):10040-6 (Pubitemid 39492027)
99. Mae M, El Andaloussi S, Lundin P, et al. A stearylated CPP for delivery of splice correcting oligonucleotides using a non-covalent co-incubation strategy. J Control Release 2009;134(3):221-7
100. Morris MC, Vidal P, Chaloin L, et al. A new peptide vector for efficient delivery of oligonucleotides into mammalian cells. Nucleic Acids Res 1997;25(14):2730-6 (Pubitemid 27299785)
101. Choi YS, Lee JY, Suh JS, et al. The systemic delivery of siRNAs by a cell penetrating peptide, low molecular weight protamine. Biomaterials 2010;31(6):1429-43
102. Muratovska A, Lightowlers RN, Taylor RW, et al. Targeting peptide nucleic acid (PNA) oligomers to mitochondria within cells by conjugation to lipophilic cations: Implications for mitochondrial DNA replication, expression and disease. Nucleic Acids Res 2001;29(9):1852-63 (Pubitemid 32433269)
103. Krutzfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNAs in vivo with 'antagomirs'. Nature 2005;438(7068):685-9
104. Oishi M, Nagasaki Y, Itaka K, et al. Lactosylated poly(ethylene glycol)- siRNA conjugate through acid-labile beta-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells. J Am Chem Soc 2005;127(6):1624-5 (Pubitemid 40229133)
105. Nakagawa O, Ming X, Huang L, et al. Targeted intracellular delivery of antisense oligonucleotides via conjugation with small-molecule ligands. J Am Chem Soc 2010;132(26):8848-9
106. Li SD, Chono S, Huang L. Efficient oncogene silencing and metastasis inhibition via systemic delivery of siRNA. Mol Ther 2008;16(5):942-6 (Pubitemid 351587105)
107. Boffa LC, Scarfi S, Mariani MR, et al. Dihydrotestosterone as a selective cellular/nuclear localization vector for anti-gene peptide nucleic acid in prostatic carcinoma cells. Cancer Res 2000;60(8):2258-62 (Pubitemid 30225192)
108. Fussl A, Schleifenbaum A, Goritz M, et al. Cellular uptake of PNA-terpyridine conjugates and its enhancement by Zn2+ ions. J Am Chem Soc 2006;128(18):5986-7
109. Kim SH, Jeong JH, Lee SH, et al. LHRH receptor-mediated delivery of siRNA using polyelectrolyte complex micelles self-assembled from siRNA-PEG-LHRH conjugate and PEI. Bioconjug Chem 2008;19(11):2156-62
110. Wieffer M, Maritzen T, Haucke V. SnapShot: Endocytic trafficking. Cell 2009;137(2):382 e1-3