Cellular uptake and intracellular trafficking of oligonucleotides: Implications for oligonucleotide pharmacology

Nucleic Acid Therapeutics

Volumn 24, Issue 2, 2014, Pages 101-113

  Juliano, R L ^a   Ming, Xin ^a   Carver, Kyle ^a   Laing, Brian ^a  

^a University of North Carolina at Chapel Hill   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; LIGAND; NANOCARRIER; OLIGONUCLEOTIDE; SMALL INTERFERING RNA;

CELL NUCLEUS; CONJUGATE; CYTOSOL; DRUG DELIVERY SYSTEM; DRUG UPTAKE; ENDOCYTOSIS; HUMAN; INTRACELLULAR TRANSPORT; NONHUMAN; PRIORITY JOURNAL; REVIEW;

BIOLOGICAL TRANSPORT; CAVEOLINS; CELL NUCLEUS; CLATHRIN; CYTOSOL; DRUG CARRIERS; ENDOCYTOSIS; EUKARYOTIC CELLS; GENE EXPRESSION REGULATION; HUMANS; INTEGRINS; OLIGONUCLEOTIDES, ANTISENSE; PHARMACEUTICAL VEHICLES; RECEPTOR TYROSINE KINASE-LIKE ORPHAN RECEPTORS; RNA, SMALL INTERFERING;

EID: 84896911109     PISSN: 21593337     EISSN: None     Source Type: Journal    
DOI: 10.1089/nat.2013.0463     Document Type: Review

References (154)

1. AKHTAR, S. (2010). Cationic nanosystems for the delivery of small interfering ribonucleic acid therapeutics: a focus on toxicogenomics. Expert Opin. Drug Metab. Toxicol. 6, 1347-62.
2. AKHTAR, S., and BENTER, I. F. (2007). Nonviral delivery of synthetic siRNAs in vivo. J Clin Invest 117, 3623-32.
3. ALAM, M. R., DIXIT, V., KAN, H., LI, Z. B., CHEN, X., TREJO, J., FISHER, M., and JULIANO, R. L. (2008). Intracellular delivery of an anionic antisense oligonucleotide via receptor-mediated endocytosis. Nucleic Acids Res. 36, 2764-2776.
4. ALAM, M. R., MING, X., DIXIT, V., FISHER, M., CHEN, X., and JULIANO, R. L. (2010). The biological effect of an antisense oligonucleotide depends on its route of endocytosis and trafficking. Oligonucleotides 20, 103-109.
5. ALAM, M. R., MING, X., FISHER, M., LACKEY, J. G., RAJEEV, K. G., MANOHARAN, M., and JULIANO, R. L. (2011). Multivalent cyclic RGD conjugates for targeted delivery of small interfering RNA. Bioconjug. Chem. 22, 1673-81.
6. ALAM, M. R., MING, X., NAKAGAWA, O., JIN, J., and JULIANO, R. L. (2013). Covalent conjugation of oligonucleotides with cell-targeting ligands. Bioorg. Med. Chem. 21, 6217-6223.
7. APLIN, A. E., STEWART, S. A., ASSOIAN, R. K., and JULIANO, R. L. (2001). Integrin-mediated adhesion regulates ERK nuclear translocation and phosphorylation of Elk-1. J Cell Biol. 153, 273-282.
8. ARMBRUSTER, B. N., and ROTH, B. L. (2005). Mining the receptorome. J. Biol. Chem. 280, 5129-5132.
9. BENIMETSKAYA, L., LOIKE, J. D., KHALED, Z., LOIKE, G., SILVERSTEIN, S. C., CAO, L., EL KHOURY, J., CAI, T. Q., and STEIN, C. A. (1997). Mac-1 (CD11b/CD18) is an oligodeoxynucleotide-binding protein. Nat. Med. 3, 414-420.
10. BENNETT, C. F., and SWAYZE, E. E. (2010). RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol. 50, 259-293.
11. BOBRIE, A., COLOMBO, M., RAPOSO, G., and THERY, C. (2011). Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12, 1659-1668.
12. BRETSCHER M. S. (1992). Circulating integrins: alpha 5 beta 1, alpha 6 beta 4 and Mac-1, but not alpha 3 beta 1, alpha 4 beta 1 or LFA-1. EMBO J 11, 405-410.
13. BRODEUR, G. M., MINTURN, J. E., HO, R., SIMPSON, A. M., IYER, R., VARELA, C. R., LIGHT, J. E., KOLLA, V., and EVANS, A. E. (2009). Trk receptor expression and inhibition in neuroblastomas. Clin. Cancer Res. 15, 3244-3250.
14. BURNETT, J. C., and ROSSI, J. J. (2012). RNA-based therapeutics: current progress and future prospects. Chem. Biol. 19, 60-71.
15. BUTLER, M., CROOKE, R. M., GRAHAM, M. J., LEMONIDIS, K. M. LOUGHEED, M., MURRAY, S. F., WITCHELL, D., STEINBRECHER, U., and BENNETT, C. F. (2000). Phosphorothioate oligodeoxynucleotides distribute similarly in class A scavenger receptor knockout and wild-type mice. J. Pharmacol. Exp. Ther. 292, 489-496.
16. BUTLER, M., STECKER, K., and BENNETT, C. F. (1997). Cellular distribution of phosphorothioate oligodeoxynucleotides in normal rodent tissues. Lab. Invest. 77, 379-388.
17. CABRERA-VERA, T. M., VANHAUWE, J., THOMAS, T. O., MEDKOVA, M., PREININGER, A., MAZZONI, M. R., and HAMM, H. E. (2003). Insights into G protein structure, function, and regulation. Endocr. Rev. 24, 765-781.
18. CAI, H., REINISCH, K., and FERRO-NOVICK, S. (2007). Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle. Dev. Cell 12, 671-682.
19. CASWELL, P. T., CHAN, M., LINDSAY, A. J., MCCAFFREY, M. W., BOETTIGER, D., and NORMAN, J. C. (2008). Rabcoupling protein coordinates recycling of alpha5beta1 integrin and EGFR1 to promote cell migration in 3D microenvironments. J. Cell Biol. 183, 143-155.
20. CASWELL, P. T., VADREVU, S., and NORMAN, J. C. (2009). Integrins: masters and slaves of endocytic transport. Nat. Rev. Mol. Cell Biol. 10, 843-853.
21. CHOI, C. H., HAO, L., NARAYAN, S. P., AUYEUNG, E., and MIRKIN, C. A. (2013). Mechanism for the endocytosis of spherical nucleic acid nanoparticle conjugates. Proc. Natl. Acad. Sci. U. S. A. 110, 7625-7630.
22. CIRAK, S., ARECHAVALA-GOMEZA, V., GUGLIERI, M., FENG, L., TORELLI, S., ANTHONY, K., ABBS, S., GARRALDA, M. E., BOURKE, J., WELLS, D. J. et al. (2011). Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 378, 595-605.
23. CLAGUE, M. J., LIU, H., and URBE, S. (2012). Governance of endocytic trafficking and signaling by reversible ubiquitylation. Dev. Cell 23, 457-467.
24. CORNELIO, D. B., ROESLER, R., and SCHWARTSMANN, G. (2007). Gastrin-releasing peptide receptor as a molecular target in experimental anticancer therapy. Ann. Oncol. 18, 1457-1466.
25. DAS, I., DESIRE, J., MANVAR, D., BAUSSANNE, I., PANDEY, V. N., and DECOUT, J. L. (2012). A peptide nucleic acid-aminosugar conjugate targeting transactivation response element of HIV-1 RNA genome shows a high bioavailability in human cells and strongly inhibits tat-mediated transactivation of HIV-1 transcription. J. Med. Chem. 55, 6021-6032.
26. DASSIE, J. P., LIU, X. Y., THOMAS, G. S., WHITAKER, R. M., THIEL, K. W., STOCKDALE, K. R., MEYERHOLZ, D. K., MCCAFFREY, A. P., MCNAMARA, J. O., 2nd, and GIANGRANDE, P. H. (2009). Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMAexpressing tumors. Nat. Biotechnol. 27, 839-849.
27. DE GIER, J. (1993). Osmotic behaviour and permeability properties of liposomes. Chem. Phys. Lipids 64, 187-196.
28. DEAMER, D. W., and BRAMHALL, J. (1986). Permeability of lipid bilayers to water and ionic solutes. Chem. Phys. Lipids 40, 167-188.
29. DELEAVEY, G. F., WATTS, J. K., and DAMHA, M. J. (2009). Chemical modification of siRNA. Curr. Protoc. Nucleic Acid Chem. Chapter 16, Unit 16. 3.
30. DESGROSELLIER, J. S., and CHERESH, D. A. (2010). Integrins in cancer: biological implications and therapeutic opportunities. Nat. Rev. Cancer 10, 9-22.
31. DOHERTY, G. J., and MCMAHON, H. T. (2009). Mechanisms of endocytosis. Annu. Rev. Biochem. 78, 857-902.
32. DRAKE, M. T., SHENOY, S. K., and LEFKOWITZ, R. J. (2006). Trafficking of G protein-coupled receptors. Circ. Res. 99, 570-582.
33. DUXBURY, M. S., ASHLEY, S. W., and WHANG, E. E. (2005). RNA interference: a mammalian SID-1 homologue enhances siRNA uptake and gene silencing efficacy in human cells. Biochem. Biophys. Res. Commun. 331, 459-463.
34. EDIN, M. L., and JULIANO, R. L. (2005). Raf-1 serine 338 phosphorylation plays a key role in adhesion-dependent activation of extracellular signal-regulated kinase by epidermal growth factor. Mol. Cell Biol. 25, 4466-4475.
35. FAUSTER, K., HARTL, M., SANTNER, T., AIGNER, M., KREUTZ, C., BISTER, K., ENNIFAR, E., and MICURA, R. (2012). 2-Azido RNA, a versatile tool for chemical biology: synthesis, X-ray structure, siRNA applications, click labeling. ACS Chem. Biol. 7, 581-589.
36. FELBER, A. E., BAYO-PUXAN, N., DELEAVEY, G. F., CASTAGNER, B., DAMHA, M. J., and LEROUX, J. C. (2012). The interactions of amphiphilic antisense oligonucleotides with serum proteins and their effects on in vitro silencing activity. Biomaterials 33, 5955-5965.
37. FILMORE, D. (2004). Its a GPCR world. Mod. Drug Discovery 7, 24-28.
38. GARRISON, J. C., ROLD, T. L., SIECKMAN, G. L., FIGUEROA, S. D., VOLKERT, W. A., JURISSON, S. S., and HOFFMAN, T. J. (2007). In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: side-by-side comparison of the CB-TE2A and DOTA chelation systems. J. Nucl. Med. 48, 1327-1337.
39. GEARY, R. S. (2009). Antisense oligonucleotide pharmacokinetics and metabolism. Expert Opin. Drug Metab. Toxicol. 5, 381-391.
40. GILLERON, J., QUERBES, W., ZEIGERER, A., BORODOVSKY, A., MARSICO, G., SCHUBERT, U., MANYGOATS, K., SEIFERT, S., ANDREE, C., STOTER, M., et al. (2013). Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat. Biotechnol. 31, 638-646.
41. GILMAN, A. G. (1995). Nobel lecture. G proteins and regulation of adenylyl cyclase. Biosci. Rep. 15, 65-97.
42. GOH, L. K., HUANG, F., KIM, W., GYGI, S., and SORKIN, A. (2010). Multiple mechanisms collectively regulate clathrinmediated endocytosis of the epidermal growth factor receptor. J. Cell Biol. 189, 871-883.
43. GURTOVENKO, A. A., ANWAR, J., and VATTULAINEN, I. (2010). Defect-mediated trafficking across cell membranes: insights from in silico modeling. Chem. Rev. 110, 6077-6103.
44. HANSS, B., LEAL-PINTO, E., TEIXEIRA, A., CHRISTIAN, R. E., SHABANOWITZ, J., HUNT, D. F., and KLOTMAN, P. E. (2002). Cytosolic malate dehydrogenase confers selectivity of the nucleic acid-conducting channel. Proc. Natl. Acad. Sci. U. S. A. 99, 1707-1712.
45. HANYALOGLU, A. C., and VON ZASTROW, M. (2008). Regulation of GPCRs by endocytic membrane trafficking and its potential implications. Annu. Rev. Pharmacol. Toxicol. 48, 537-568.
46. HENNE, W. M., BUCHKOVICH, N. J., and EMR, S. D. (2011). The ESCRT pathway. Dev. Cell 21, 77-91.
47. HOPKINS, A. L., and GROOM, C. R. (2002). The druggable genome. Nat. Rev. Drug Discov. 1, 727-730.
48. HOUSTON, D., OHNO, M., NICHOLAS, R. A., JACOBSON, K. A., and HARDEN, T. K. (2006). [32P]2-iodo-N6-methyl-(N)-methanocarba-2-deoxyadenosine-3,5- bisphosphate ([32P] MRS2500), a novel radioligand for quantification of native P2Y1 receptors. Br. J. Pharmacol. 147, 459-467.
49. HOWES, M. T., MAYOR, S., and PARTON, R. G. (2010). Molecules, mechanisms, and cellular roles of clathrin-independent endocytosis. Curr. Opin. Cell Biol. 22, 519-527.
50. HUGHSON, F. M., and REINISCH, K. M. (2010). Structure and mechanism in membrane trafficking. Curr. Opin. Cell Biol. 22, 454-460.
51. HUOTARI, J., and HELENIUS, A. (2011). Endosome maturation. EMBO J. 30, 3481-3500.
52. HUTAGALUNG, A. H., and NOVICK, P. J. (2011). Role of Rab GTPases in membrane traffic and cell physiology. Physiol. Rev. 91, 119-149.
53. HWANG, J. Y., PARK, J., KANG, B. J., LUBOW, D. J., CHU, D., FARKAS, D. L., SHUNG, K. K., and MEDINA-KAUWE, L. K. (2012). Multimodality imaging in vivo for preclinical assessment of tumor-targeted doxorubicin nanoparticles. PLoS One 7, e34463.
54. HYNES, N. E., and LANE, H. A. (2005). ERBB receptors and cancer: the complexity of targeted inhibitors. Nat. Rev. Cancer 5, 341-354.
55. HYNES, R. O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell 110, 673-687.
56. IMAI, Y., LEUNG, C. K., FRIESEN, H. G., and SHIU, R. P. (1982). Epidermal growth factor receptors and effect of epidermal growth factor on growth of human breast cancer cells in longterm tissue culture. Cancer Res. 42, 4394-4398.
57. JOHANNES, L., and WUNDER, C (2011). Retrograde transport: two (or more) roads diverged in an endosomal tree? Traffic 12, 956-962.
58. JULIANO, R., BAUMAN, J., KANG, H., and MING, X. (2009). Biological barriers to therapy with antisense and siRNA oligonucleotides. Mol. Pharm. 6, 686-695.
59. JULIANO, R. L., ALAHARI, S., YOO, H., KOLE, R., and CHO, M. (1999). Antisense pharmacodynamics: critical issues in the transport and delivery of antisense oligonucleotides. Pharm. Res. 16, 494-502.
60. JULIANO, R. L., MING, X., and NAKAGAWA, O. (2012a). Cellular uptake and intracellular trafficking of antisense and siRNA oligonucleotides. Bioconjug. Chem. 23, 147-157.
61. JULIANO, R. L., MING, X., and NAKAGAWA, O. (2012b). The chemistry and biology of oligonucleotide conjugates. Acc. Chem. Res. 45, 1067-1076.
62. JULIANO, R. L., REDDIG, P., ALAHARI, S., EDIN, M., HOWE, A., and APLIN, A. (2004). Integrin regulation of cell signalling and motility. Biochem. Soc. Trans. 32, 443-446.
63. KABANOV, A. V., and VINOGRADOV, S. V. (2009). Nanogels as pharmaceutical carriers: finite networks of infinite capabilities. Angew Chem. Int. Ed. Engl. 48, 5418-5429.
64. KANEDA, M. M., SASAKI, Y., LANZA, G. M., MILBRANDT, J., and WICKLINE, S. A. (2010). Mechanisms of nucleotide trafficking during siRNA delivery to endothelial cells using perfluorocarbon nanoemulsions. Biomaterials 31, 3079-3086.
65. KARJALAINEN, M., KAKKONEN, E., UPLA, P., PALORANTA, H., KANKAANPAA, P., LIBERALI, P., RENKEMA, G. H., HYYPIA, T., HEINO, J., and MARJOMAKI, V. (2008). A Raft-derived, Pak1-regulated entry participates in alpha2beta1 integrin-dependent sorting to caveosomes. Mol. Biol. Cell 19, 2857-2869.
66. KAWAI, T., and AKIRA, S. (2011). Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34, 637-650.
67. KENDALL, G. C., MOKHONOVA, E. I., MORAN, M., SEJBUK, N. E., WANG, D. W., SILVA, O., WANG, R. T., MARTINEZ, L., LU, Q. L., DAMOISEAUX, R., et al. (2012). Dantrolene enhances antisense-mediated exon skipping in human and mouse models of Duchenne muscular dystrophy. Sci. Transl. Med. 4, 164ra160.
68. KERR, M. C., and TEASDALE, R. D. (2009). Defining macropinocytosis. Traffic 10, 364-371.
69. KIM, C., YE, F., and GINSBERG, M. H. (2011). Regulation of integrin activation. Annu. Rev. Cell Dev. Biol. 27, 321-345.
70. KIMPLE, A. J., BOSCH, D. E., GIGUERE, P. M., and SIDEROVSKI, D. P. (2011). Regulators of G-protein signaling and their Galpha substrates: promises and challenges in their use as drug discovery targets. Pharmacol. Rev. 63, 728-749.
71. KIRPOTIN, D. B., DRUMMOND, D. C., SHAO, Y., SHALABY, M. R., HONG, K., NIELSEN, U. B., MARKS, J. D., BENZ, C. C., and PARK, J. W. (2006). Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res. 66, 6732-6740.
72. KOCH, S., and CLAESSON-WELSH, L. (2012). Signal transduction by vascular endothelial growth factor receptors. Cold Spring Harb. Perspect. Med. 2, a006502.
73. KOLE R., KRAINER A. R., ALTMAN S. (2012). RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nat. Rev. Drug Discov. 11, 125-1240.
74. KOLLER, E., VINCENT, T. M., CHAPPELL, A., DE, S., MANOHARAN, M., and BENNETT, C. F. (2011). Mechanisms of single-stranded phosphorothioate modified antisense oligonucleotide accumulation in hepatocytes. Nucleic Acids Res. 39, 4795-4807.
75. KORTYLEWSKI, M., SWIDERSKI, P., HERRMANN, A., WANG, L., KOWOLIK, C., KUJAWSKI, M., LEE, H., SCUTO, A., LIU, Y., YANG, C., et al. (2009). In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nat. Biotechnol. 27, 925-932.
76. KRAUSE, D. S., and VAN ETTEN, R. A. (2005). Tyrosine kinases as targets for cancer therapy. N. Engl. J. Med. 353, 172-187.
77. KRUTZFELDT, J., RAJEWSKY, N., BRAICH, R., RAJEEV, K. G., TUSCHL, T., MANOHARAN, M., and STOFFEL, M. (2005). Silencing of microRNAs in vivo with 'antagomirs'. Nature 438, 685-689.
78. LAJOIE, P., and NABI, I. R. (2010). Lipid rafts, caveolae, and their endocytosis. Int. Rev. Cell Mol. Biol. 282, 135-163.
79. LEE, C. H., LEE, Y. J., KIM, J. H., LIM, J. H., KIM, J. H., HAN, W., LEE, S. H., NOH, G. J., and LEE, S. W. (2013). Inhibition of hepatitis C virus (HCV) replication by specific RNA aptamers against HCV NS5B RNA replicase. J. Virol. 87, 7064-7074.
80. LEMMON, M. A., and SCHLESSINGER, J. (2010). Cell signaling by receptor tyrosine kinases. Cell 141, 1117-1134.
81. LEVITZKI, A., ATLAS, D., and STEER, M. L. (1974). The binding characteristics and number of beta-adrenergic receptors on the turkey erythrocyte. Proc. Natl. Acad. Sci. U. S. A. 71, 2773-2776.
82. LI, J., WANG, Y., ZHU, Y., and OUPICKY, D. (2013). Recent advances in delivery of drug-nucleic acid combinations for cancer treatment. J. Control. Release 172, 589-600.
83. LI, S., HUANG, S., and PENG, S. B. (2005). Overexpression of G protein-coupled receptors in cancer cells: involvement in tumor progression. Int. J. Oncol. 27, 1329-1339.
84. LIU, X., WANG, Y., and HNATOWICH, D. J. (2011). A nanoparticle for tumor targeted delivery of oligomers. Methods Mol. Biol. 764, 91-105.
85. LONNBERG, H. (2009). Solid-phase synthesis of oligonucleotide conjugates useful for delivery and targeting of potential nucleic acid therapeutics. Bioconjug. Chem. 20, 1065-1094.
86. LOVE, K. T., MAHON, K. P., LEVINS, C. G., WHITEHEAD, K. A., QUERBES, W., DORKIN, J. R., QIN, J., CANTLEY, W., QIN, L. L., RACIE, T., et al. (2010). Lipid-like materials for low-dose, in vivo gene silencing. Proc. Natl. Acad. Sci. U. S. A. 107, 1864-1869.
87. LU, J. J., LANGER, R., and CHEN, J. (2009). A novel mechanism is involved in cationic lipid-mediated functional siRNA delivery. Mol. Pharm. 6, 763-771.
88. LV, H., ZHANG, S., WANG, B., CUI, S., and YAN, J. (2006). Toxicity of cationic lipids and cationic polymers in gene delivery. J. Control. Release 114, 100-109.
89. MARGADANT, C., MONSUUR, H. N., NORMAN, J. C., and SONNENBER, G A. (2011). Mechanisms of integrin activation and trafficking. Curr. Opin. Cell Biol. 23, 607-614.
90. MARLIN, F., SIMON, P., SAISON-BEHMOARAS, T., and GIOVANNANGELI, C. (2010). Delivery of oligonucleotides and analogues: the oligonucleotide conjugate-based approach. Chembiochem 11, 1493-500.
91. MCNAMARA, J. O., 2nd, ANDRECHEK, E. R., WANG, Y., VILES, K. D., REMPEL, R. E., GILBOA, E., SULLENGER, B. A., and GIANGRANDE, P. H. (2006). Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat. Biotechnol. 24, 1005-1015.
92. METTLEN, M., PUCADYIL, T., RAMACHANDRAN, R., and SCHMID, S. L. (2009). Dissecting dynamin's role in clathrinmediated endocytosis. Biochem. Soc. Trans. 37, 1022-1026.
93. MIACZYNSKA, M., and BAR-SAGI, D. (2010). Signaling endosomes: seeing is believing. Curr. Opin. Cell Biol. 22, 535-540.
94. MILLARD, M., ODDE, S., and NEAMATI, N. (2011). Integrin targeted therapeutics. Theranostics 1, 154-188.
95. MING, X. (2011). Cellular delivery of siRNA and antisense oligonucleotides via receptor-mediated endocytosis. Expert Opin. Drug Deliv. 8, 435-449.
96. MING, X., ALAM, M. R., FISHER, M., YAN, Y., CHEN, X., and JULIANO, R. L. (2010). Intracellular delivery of an antisense oligonucleotide via endocytosis of a G protein-coupled receptor. Nucleic Acids Res. 38, 6567-6576.
97. MING, X., CARVER, K., FISHER, M., NOEL, R., CINTRAT, J. C., GILLET, D., BARBIER, J., CAO, C., BAUMAN, J., and JULIANO, R. L. (2013a). The small molecule Retro-1 enhances the pharmacological actions of antisense and splice switching oligonucleotides. Nucleic Acids Res. 41, 3673-3687.
98. MING, X., CARVER, K., and WU, L. (2013b). Albumin-based nanoconjugates for targeted delivery of therapeutic oligonucleotides. Biomaterials 34, 7939-7949.
99. MING, X., SATO, K., and JULIANO, R. L. (2011). Unconventional internalization mechanisms underlying functional delivery of antisense oligonucleotides via cationic lipoplexes and polyplexes. J. Control. Release 153, 83-92.
100. MOLITORIS, B. A., DAGHER, P. C., SANDOVAL, R. M., CAMPOS, S. B., ASHUSH, H., FRIDMAN, E., BRAFMAN, A., FAERMAN, A., ATKINSON, S. J., THOMPSON, J. D., et al. (2009). siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury. J. Am. Soc. Nephrol. 20, 1754-1764.
101. MOSSALAM, M., DIXON, A. S., and LIM, C. S. (2010). Controlling subcellular delivery to optimize therapeutic effect. Ther. Deliv. 1, 169-193.
102. MULGREW, K., KINNEER, K., YAO, X. T., WARD, B. K., DAMSCHRODER, M. M., WALSH, B., MAO, S. Y., GAO, C., KIENER, P. A., COATS, S., et al. (2006). Direct targeting of alphavbeta3 integrin on tumor cells with a monoclonal antibody, Abegrin. Mol. Cancer Ther. 5, 3122-3129.
103. NAKAGAWA, O., MING, X., HUANG, L., and JULIANO, R. L. (2010). Targeted intracellular delivery of antisense oligonucleotides via conjugation with small-molecule ligands. J. Am. Chem. Soc. 132, 8848-8849.
104. NAPIONE, L., PAVAN, S., VEGLIO, A., PICCO, A., BOFFETTA, G., CELANI, A., SEANO, G., PRIMO, L., GAMBA, A., and BUSSOLINO, F. (2012). Unraveling the influence of endothelial cell density on VEGF-A signaling. Blood 119, 5599-5607.
105. NGUYEN, J., and SZOKA, F. C. (2012). Nucleic acid delivery: the missing pieces of the puzzle? Acc. Chem. Res. 45, 1153-1162.
106. NIU, G., and CHEN, X. (2011). Why integrin as a primary target for imaging and therapy. Theranostics 1, 30-47.
107. OVERHOFF, M., and SCZAKIEL, G. (2005). Phosphorothioatestimulated uptake of short interfering RNA by human cells. EMBO Rep. 6, 1176-1181.
108. PARACHONIAK, C. A., and PARK, M. (2012). Dynamics of receptor trafficking in tumorigenicity. Trends Cell Biol. 22, 231-240.
109. PARSONS, J. T. (2003). Focal adhesion kinase: the first ten years. J. Cell Sci. 116, 1409-1416.
110. PASTOR, F., KOLONIAS, D., GIANGRANDE, P. H., and GILBOA, E. (2010). Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay. Nature 465, 227-230.
111. PATEL, P. C., GILJOHANN, D. A., DANIEL, W. L., ZHENG, D., PRIGODICH, A. E., and MIRKIN, C. A. (2010). Scavenger receptors mediate cellular uptake of polyvalent oligonucleotidefunctionalized gold nanoparticles. Bioconjug. Chem. 21, 2250-2256.
112. PETROS, R. A., and DESIMONE, J. M. (2010). Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 9, 615-227.
113. PFEFFER, S. R. (2007). Unsolved mysteries in membrane traffic. Annu. Rev. Biochem. 76, 629-645.
114. PFEFFER, S. R. (2013). Rab GTPase regulation of membrane identity. Curr. Opin. Cell Biol. 25, 414-419.
115. PHELPS, K., MORRIS, A., and BEAL, P. A. (2012). Novel modifications in RNA. ACS Chem. Biol. 7, 100-109.
116. PIERSCHBACHER, M. D., and RUOSLAHTI, E. (1984). Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature 309, 30-33.
117. POST, S. R., HILAL-DANDAN, R., URASAWA, K., BRUNTON, L. L., and INSEL, P. A. (1995). Quantification of signalling components and amplification in the beta-adrenergic-receptoradenylate cyclase pathway in isolated adult rat ventricular myocytes. Biochem J. 311, 75-80.
118. RAO, H., SAWANT, A. A., TANPURE, A. A., and SRIVATSAN, S. G. (2012). Posttranscriptional chemical functionalization of azide-modified oligoribonucleotides by bioorthogonal click and Staudinger reactions. Chem. Commun. (Camb. ) 48, 498-500.
119. ROBBINS, M., JUDGE, A., and MACLACHLAN, I. (2009). siRNA and innate immunity. Oligonucleotides 19, 89-102.
120. SAHAY, G., QUERBES, W., ALABI, C., ELTOUKHY, A., SARKAR, S., ZURENKO, C., KARAGIANNIS, E., LOVE, K., CHEN, D., ZONCU, R., et al. (2013). Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat. Biotechnol. 31, 653-658.
121. SCHWARTZ, M. A. (2010). Integrins and extracellular matrix in mechanotransduction. Cold Spring Harb. Perspect. Biol. 2, a005066.
122. SCZEKAN, M. M., and JULIANO, R. L. (1990). Internalization of the fibronectin receptor is a constitutive process. J Cell Physiol 142, 574-80.
123. SHEPARD, H. M., JIN, P., SLAMON, D. J., PIROT, Z., and MANEVAL, D. C. (2008). Herceptin. Handb. Exp. Pharmacol. 181, 183-219.
124. SHIMAOKA, M., and SPRINGER, T. A. (2003). Therapeutic antagonists and conformational regulation of integrin function. Nat. Rev. Drug Discov. 2, 703-716.
125. SHUKLA A. K., XIAO K., LEFKOWITZ R. J. (2011). Emerging paradigms of beta-arrestin-dependent seven transmembrane receptor signaling. Trends Biochem. Sci. 36, 457-469.
126. SINGH, Y., MURAT, P., and DEFRANCQ, E. (2010). Recent developments in oligonucleotide conjugation. Chem. Soc. Rev. 39, 2054-2070.
127. SORKIN, A., and VON ZASTROW, M. (2009). Endocytosis and signalling: intertwining molecular networks. Nat. Rev. Mol. Cell Biol. 10, 609-622.
128. SPANG, A. (2009). On vesicle formation and tethering in the ERGolgi shuttle. Curr. Opin. Cell. Biol. 21, 531-536.
129. STECHMANN, B., BAI, S. K., GOBBO, E., LOPEZ, R., MERER, G., PINCHARD, S., PANIGAI, L., TENZA, D., RAPOSO, G., BEAUMELLE, B., et al. (2010). Inhibition of retrograde transport protects mice from lethal ricin challenge. Cell 141, 231-242.
130. STEIN, C. A., HANSEN, J. B., LAI, J., WU, S., VOSKRESENSKIY, A., HOG, A., WORM, J., HEDTJARN, M., SOULEIMANIAN, N., MILLER, P., et al. (2010). Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents. Nucleic Acids Res. 38, e3.
131. STENMARK, H. (2009). Rab GTPases as coordinators of vesicle traffic. Nat. Rev. Mol. Cell. Biol. 10, 513-525.
132. STREULI, C. H., and AKHTAR, N. (2009). Signal co-operation between integrins and other receptor systems. Biochem J 418, 491-506.
133. SZABO, A. M., HOWELL, N. R., PELLEGRINI, P., GREGURIC, I., and KATSIFIS, A. (2012). Development and validation of competition binding assays for affinity to the extracellular matrix receptors, alpha(v)beta(3) and alpha(IIb)beta(3) integrin. Anal. Biochem. 423, 70-77.
134. TAMURA, A., and NAGASAKI, Y. (2010). Smart siRNA delivery systems based on polymeric nanoassemblies and nanoparticles. Nanomedicine (Lond. ) 5, 1089-1102.
135. TOHIDKIA, M. R., BARAR, J., ASADI, F., and OMIDI, Y. (2012). Molecular considerations for development of phage antibody libraries. J. Drug Target 20, 195-208.
136. TSANG, S. Y., MOORE, J. C., HUIZEN, R. V., CHAN, C. W., and LI, R. A. (2007). Ectopic expression of systemic RNA interference defective protein in embryonic stem cells. Biochem. Biophys. Res. Commun. 357, 480-486.
137. TSENG, Y. C., MOZUMDAR, S., and HUANG, L. (2009). Lipidbased systemic delivery of siRNA. Adv. Drug Deliv. Rev. 61, 721-731.
138. UGARTE-URIBE, B., GRIJALVO, S., BUSTO, J. V., MARTIN, C., ERITJA, R., GONI, F. M., and ALKORTA, I. (2013). Doubletailed lipid modification as a promising candidate for oligonucleotide delivery in mammalian cells. Biochim. Biophys. Acta 1830, 4872-4884.
139. UNO, Y., PIAO, W., MIYATA, K., NISHINA, K., MIZUSAWA, H., and YOKOTA, T. (2011). High-density lipoprotein facilitates in vivo delivery of alpha-tocopherol-conjugated shortinterfering RNA to the brain. Hum. Gene Ther. 22, 711-719.
140. VARKOUHI, A. K., SCHOLTE, M., STORM, G., and HAISMA, H. J. (2011). Endosomal escape pathways for delivery of biologicals. J. Control. Release 151, 220-228.
141. VON KLEIST, L., and HAUCKE, V. (2012). At the crossroads of chemistry and cell biology: inhibiting membrane traffic by small molecules. Traffic 13, 495-504.
142. WATTS, J. K., DELEAVEY, G. F., and DAMHA, M. J. (2008). Chemically modified siRNA: tools and applications. Drug Discov. Today 13, 842-855.
143. WHEELER, L. A., TRIFONOVA, R., VRBANAC, V., BASAR, E., MCKERNAN, S., XU, Z., SEUNG, E., DERUAZ, M., DUDEK, T., EINARSSON, J. I., et al. (2011). Inhibition of HIV transmission in human cervicovaginal explants and humanized mice using CD4 aptamer-siRNA chimeras. J. Clin. Invest. 121, 2401-2412.
144. WHITEHEAD, K. A., LANGER, R., and ANDERSON, D. G. (2009). Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 8, 129-138.
145. WICKSTROM, S. A., and FASSLER, R. (2011). Regulation of membrane traffic by integrin signaling. Trends Cell Biol. 21, 266-273.
146. WINSTON, W. M., SUTHERLIN, M., WRIGHT, A. J., FEINBERG, E. H., and HUNTER, C. P. (2007). Caenorhabditis elegans SID-2 is required for environmental RNA interference. Proc. Natl. Acad. Sci. U. S. A. 104, 10565-10570.
147. WINZ, M. L., SAMANTA, A., BENZINGER, D., and JASCHKE, A. (2012). Site-specific terminal and internal labeling of RNA by poly(A) polymerase tailing and copper-catalyzed or copper-free strain-promoted click chemistry. Nucleic Acids Res. 40, e78.
148. WOLFRUM, C., SHI, S., JAYAPRAKASH, K. N., JAYARAMAN, M., WANG, G., PANDEY, R. K., RAJEEV, K. G., NAKAYAMA, T., CHARRISE, K., NDUNGO, E. M., et al. (2007). Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat. Biotechnol. 25, 1149-1157.
149. XU, S., OLENYUK, B. Z., OKAMOTO, C. T., and HAMM-ALVAREZ, S. F. (2013). Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances. Adv. Drug Deliv. Rev. 65, 121-138.
150. YAMADA, T., PENG, C. G., MATSUDA, S., ADDEPALLI, H., JAYAPRAKASH, K. N., ALAM, M. R., MILLS, K., MAIER, M. A., CHARISSE, K., SEKINE, M., et al. (2011). Versatile sitespecific conjugation of small molecules to siRNA using click chemistry. J. Org. Chem. 76, 1198-1211.
151. ZHANG, Q., HOSSAIN, D. M., NECHAEV, S., KOZLOWSKA, A., ZHANG, W., LIU, Y., KOWOLIK, C. M., SWIDERSKI, P., ROSSI, J. J., FORMAN, S., et al. (2013). TLR9-mediated siRNA delivery for targeting of normal and malignant human hematopoietic cells in vivo. Blood 121, 1304-1315.
152. ZHANG, Y., QU, Z., KIM, S., SHI, V., LIAO, B., KRAFT, P., BANDARU, R., WU, Y., GREENBERGER, L. M., and HORAK, I. D. (2011). Down-modulation of cancer targets using locked nucleic acid (LNA)-based antisense oligonucleotides without transfection. Gene Ther. 18, 326-333.
153. ZHENG, D., GILJOHANN, D. A., CHEN, D. L., MASSICH, M. D., WANG, X. Q., IORDANOV, H., MIRKIN, C. A., and PALLER, A. S. (2012). Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation. Proc. Natl. Acad. Sci. U. S. A. 109, 11975-11980.
154. ZHOU, J., and ROSSI, J. J. (2011). Cell-specific aptamer-mediated targeted drug delivery. Oligonucleotides 21, 1-10.