RNA interference trigger variants: Getting the most out of RNA for RNA interference-based therapeutics

Nucleic Acid Therapeutics

Volumn 22, Issue 3, 2012, Pages 139-146

  Snead, Nicholas M ^a   Rossi, John J ^a  

^a CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; DOUBLE STRANDED RNA; LIGAND; LIPID; LOCKED NUCLEIC ACID; MACROGOL; MESSENGER RNA; MODIFIED SMALL INTERFERING RNA; NANOPARTICLE; NUCLEIC ACID; POLYMER; SHORT HAIRPIN RNA; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; UNLOCKED NUCLEIC ACID; UNMODIFIED SMALL INTERFERING RNA; VIRUS VECTOR;

3' UNTRANSLATED REGION; 5' UNTRANSLATED REGION; AMINO ACID SUBSTITUTION; AMYLOIDOSIS; CLINICAL TRIAL (TOPIC); CONGENITAL PACHYONYCHIA; DNA VECTOR; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG FATALITY; DRUG FORMULATION; DRUG SAFETY; EBOLA HEMORRHAGIC FEVER; GENE SILENCING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERCHOLESTEROLEMIA; LOW DRUG DOSE; MELANOMA; METASTASIS; NEOPLASM; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN MODIFICATION; RESPIRATORY SYNCYTIAL VIRUS INFECTION; RETINA MACULA AGE RELATED DEGENERATION; RETINA MACULA EDEMA; REVIEW; RIBONUCLEIC ACID MODIFICATION; RNA INTERFERENCE; RNA SEQUENCE; RNA STRUCTURE; SINGLE DRUG DOSE; SOLID TUMOR; UNSPECIFIED SIDE EFFECT;

CLINICAL TRIALS AS TOPIC; HUMANS; RNA INTERFERENCE; RNA, SMALL INTERFERING;

EID: 84862317270     PISSN: 21593337     EISSN: None     Source Type: Journal    
DOI: 10.1089/nat.2012.0361     Document Type: Review

References (77)

1. AKINC, A., GOLDBERG, M., QIN, J., DORKIN, J.R., GAMBAVITALO, C., MAIER, M., et al. (2009). Development of lipidoid-siRNA formulations for systemic delivery to the liver. Mol. Ther. 17, 872-879.
2. AKINC, A., QUERBES, W., DE, S., QIN, J., FRANK-KAMENETSKY, M., JAYAPRAKASH, K.N., et al. (2010). Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol. Ther. 18, 1357-1364.
3. AKINC, A., ZUMBUEHL, A., GOLDBERG, M., LESHCHINER, E.S., BUSINI, V., HOSSAIN, N., et al. (2008). A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat. Biotechnol. 26, 561-569.
4. ALAM, M.R., MING, X., FISHER, M., LACKEY, J.G., RAJEEV, K.G., MANOHARAN, M., et al. (2011). Multivalent cyclic RGD conjugates for targeted delivery of small interfering RNA. Bioconjug. Chem. 22, 1673-1681.
5. ALEKU, M., SCHULZ, P., KEIL, O., SANTEL, A., SCHAEPER, U., DIECKHOFF, B., et al. (2008). Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression. Cancer Res. 68, 9788-9798.
6. ALLERSON, C.R., SIOUFI, N., JARRES, R., PRAKASH, T.P., NAIK, N., BERDEJA, A., et al. (2005). Fully 2′-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA. J. Med. Chem. 48, 901-904.
7. BOHLE, H., LORENZEN, N., and SCHYTH, B.D. (2011). Species specific inhibition of viral replication using dicer substrate siRNAs (DsiRNAs) targeting the viral nucleoprotein of the fish pathogenic rhabdovirus viral hemorrhagic septicemia virus (VHSV). Antiviral Res. 90, 187-194.
8. BRAMSEN, J.B., LAURSEN, M.B., DAMGAARD, C.K., LENA, S.W., BABU, B.R., WENGEL, J., et al. (2007). Improved silencing properties using small internally segmented interfering RNAs. Nucleic Acids Res. 35, 5886-5897.
9. BRAMSEN, J.B., LAURSEN, M.B., NIELSEN, A.F., HANSEN, T.B., BUS, C., LANGKJAER, N., et al. (2009). A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity. Nucleic Acids Res. 37, 2867-2881.
10. BRAMSEN, J.B., PAKULA, M.M., HANSEN, T.B., BUS, C., LANGKJAER, N., ODADZIC, D., et al. (2010). A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects. Nucleic Acids Res. 38, 5761-573.
11. BUI, J.D., and SCHREIBER, R.D. (2007). Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Curr. Opin. Immunol. 19, 203-208.
12. CHANG, C.I., LEE, T.Y., KIM, S., SUN, X., HONG, S.W., YOO, J.W., et al. (2012a). Enhanced intracellular delivery and multitarget gene silencing triggered by tripodal RNA structures. J. Gene Med. 14, 138-146.
13. CHANG, C.I., LEE, T.Y., YOO, J.W., SHIN, D., KIM, M., KIM, S., et al. (2012b). Branched, tripartite-interfering RNAs silence multiple target genes with long guide strands. Nucleic Acid Ther. 22, 30-39.
14. CHANG, C.I., YOO, J.W., HONG, S.W., LEE, S.E., KANG, H.S., SUN, X., et al. (2009). Asymmetric shorter-duplex siRNA structures trigger efficient gene silencing with reduced non-specific effects. Mol. Ther. 17, 725-32.
15. CHEN, P. Y., WEINMANN, L., GAIDATZIS, D., PEI, Y., ZAVOLAN, M., TUSCHL, T., et al. (2008). Strand-specific 5′-Omethylation of siRNA duplexes controls guide strand selection and targeting specificity. RNA 14, 263-274.
16. CHORN, G., ZHAO, L., SACHS, A.B., FLANAGAN, W.M., and LIM, L.P. (2010). Persistence of seed-based activity following segmentation of a microRNA guide strand. RNA 16, 2336-2340.
17. CHU, C.Y., and RANA, T.M. (2008). Potent RNAi by short RNA triggers. RNA 14, 1714-1719.
18. COLLINGWOOD, M.A., ROSE, S.D., HUANG, L., HILLIER, C., AMARZGUIOUI, M., WIIGER, M.T., et al. (2008). Chemical modification patterns compatible with high potency dicer-substrate small interfering RNAs. Oligonucleotides 18, 187-200.
19. DANDE, P., PRAKASH, T.P., SIOUFI, N., GAUS, H., JARRES, R., BERDEJA, A., et al. (2006). Improving RNA interference in mammalian cells by 4′-thio-modified small interfering RNA (siRNA): effect on siRNA activity and nuclease stability when used in combination with 2′-O-alkyl modifications. J.Med. Chem. 49, 1624-1634.
20. DARNIOT, M., SCHILDGEN, V., SCHILDGEN, O., SPROAT, B., KLEINES, M., DITT, V., et al. (2012). RNA interference in vitro and in vivo using DsiRNA targeting the nucleocapsid N mRNA of human metapneumovirus. Antiviral Res. 93, 364-373.
21. DAVIS, M.E., ZUCKERMAN, J.E., CHOI, C.H., SELIGSON, D., TOLCHER, A., ALABI, C.A., et al. (2010). Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464, 1067-1070.
22. DE FOUGEROLLES, A., VORNLOCHER, H. P., MARAGANORE, J., and LIEBERMAN, J. (2007). Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev. Drug Discov. 6, 443-453.
23. DEJNEKA, N.S., WAN, S., BOND, O.S., KORNBRUST, D.J., and REICH, S.J. (2008). Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes. Mol. Vis. 14, 997-1005.
24. DOHMEN, C., FROHLICH, T., LACHELT, U., ROHL, I., VORNLOCHER, H.-P., HADWIGER, P., et al. (2012). Defined Folate-PEG-siRNA Conjugates for Receptor-specific Gene Silencing. Mol. Ther. Nucleic Acids 1, e7.
25. DORE-SAVARD, L., ROUSSY, G., DANSEREAU, M.A., COLLINGWOOD, M.A., LENNOX, K.A., ROSE, S.D., et al. (2008). Central delivery of Dicer-substrate siRNA: a direct application for pain research. Mol. Ther. 16, 1331-1339.
26. DOWLER, T., BERGERON, D., TEDESCHI, A.L., PAQUET, L., FERRARI, N., and DAMHA, M.J. (2006). Improvements in siRNA properties mediated by 2′-deoxy-2′-fluoro-beta-D-ara-binonucleic acid (FANA). Nucleic Acids Res. 34, 1669-1675.
27. ELBASHIR, S.M., HARBORTH, J., LENDECKEL, W., YALCIN, A., WEBER, K., and TUSCHL, T. (2001). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494-498.
28. ELMEN, J., THONBERG, H., LJUNGBERG, K., FRIEDEN, M., WESTERGAARD, M., XU, Y., et al. (2005). Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Res. 33, 439-447.
29. FIRE, A., XU, S., MONTGOMERY, M.K., KOSTAS, S.A., DRIVER, S.E., and MELLO, C.C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811.
30. FORD, L.P., and TOLOUE, M.M. (2010). Delivery of RNAi mediators. Wiley Interdiscip. Rev. RNA 1, 341-350.
31. FOSTER, D.J., BARROS, S., DUNCAN, R., SHAIKH, S., CANTLEY, W., DELL, A., et al. (2012). Comprehensive evaluation of canonical versus Dicer-substrate siRNA in vitro and in vivo. RNA 18, 557-568.
32. GUO, P. (2010). The emerging field of RNA nanotechnology. Nat. Nanotechnol. 5, 833-842.
33. GUO, S., HUANG, F., and GUO, P. (2006). Construction of folate-conjugated pRNA of bacteriophage phi29 DNA packaging motor for delivery of chimeric siRNA to nasopharyngeal carcinoma cells. Gene Ther. 13, 814-820.
34. HICKERSON, R.P., FLORES, M.A., LEAKE, D., LARA, M.F., CONTAG, C.H., LEACHMAN, S.A., et al. (2011). Use of self-delivery siRNAs to inhibit gene expression in an organotypic pachyonychia congenita model. J. Invest. Dermatol. 131, 1037-1044.
35. HICKERSON, R.P., SMITH, F.J., REEVES, R.E., CONTAG, C.H., LEAKE, D., LEACHMAN, S.A., et al. (2008a). Single-nucleotide-specific siRNA targeting in a dominant-negative skin model. J. Invest. Dermatol. 128, 594-605.
36. HICKERSON, R.P., VLASSOV, A.V., WANG, Q., LEAKE, D., ILVES, H., GONZALEZ-GONZALEZ, E., et al. (2008b). Stability study of unmodified siRNA and relevance to clinical use. Oligonucleotides 18, 345-354.
37. HOERTER, J.A.H., KRISHNAN, V., LIONBERGER, T.A., and WALTER, N.G. (2011). siRNA-like double-stranded RNAs are specifically protected against degradation in human cell extract. PLoS One 6, e20359.
38. HOWARD, K.A., PALUDAN, S.R., BEHLKE, M.A., BESENBACHER, F., DELEURAN, B., and KJEMS, J. (2009). Chitosan/siRNA nanoparticle-mediated TNF-alpha knockdown in peritoneal macrophages for anti-inflammatory treatment in a murine arthritis model. Mol. Ther. 17, 162-168.
39. JACKSON, A.L., BURCHARD, J., LEAKE, D., REYNOLDS, A., SCHELTER, J., GUO, J., et al. (2006). Position-specific chemical modification of siRNAs reduces off-target transcript silencing. RNA 12, 1197-1205.
40. JACKSON, A.L., and LINSLEY, P.S. (2010). Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application. Nat. Rev. Drug Discov. 9, 57-67.
41. KENSKI, D.M., COOPER, A.J., LI, J.J., WILLINGHAM, A.T., HARINGSMA, H.J., YOUNG, T.A., et al. (2010). Analysis of acyclic nucleoside modifications in siRNAs finds sensitivity at position 1 that is restored by 5′-terminal phosphorylation both in vitro and in vivo. Nucleic Acids Res. 38, 660-671.
42. KENSKI, D.M., WILLINGHAM, A.T., HARINGSMA, H.J., LI, J.J., and FLANAGAN, W.M. (2012). In vivo activity and duration of short interfering RNAs containing a synthetic 5′-phosphate. Nucleic Acid Ther. 22, 90-95.
43. KHVOROVA, A., REYNOLDS, A., and JAYASENA, S.D. (2003). Functional siRNAs and miRNAs exhibit strand bias. Cell 115, 209-216.
44. KIM, D.H., BEHLKE, M.A., ROSE, S.D., CHANG, M.S., CHOI, S., and ROSSI, J.J. (2005). Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nat. Biotech. 23, 222-226.
45. KIM, D.H., and ROSSI, J.J. (2007). Strategies for silencing human disease using RNA interference. Nat. Rev. Genet. 8, 173-184.
46. KLEINMAN, M.E., KANEKO, H., CHO, W.G., DRIDI, S., FOWLER, B.J., BLANDFORD, A.D., et al. (2012). Short-interfering RNAs induce retinal degeneration via TLR3 and IRF3. Mol. Ther. 20, 101-108.
47. KLEINMAN, M.E., YAMADA, K., TAKEDA, A., CHANDRASEKARAN, V., NOZAKI, M., BAFFI, J.Z., et al. (2008). Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452, 591-597.
48. KUBO, T., TAKEI, Y., MIHARA, K., YANAGIHARA, K., and SEYAMA, T. (2012). Amino-modified and lipid-conjugated dicer-substrate siRNA enhances RNAi efficacy. Bioconjug. Chem. 23, 164-173.
49. KUBO, T., ZHELEV, Z., OHBA, H., and BAKALOVA, R. (2007). Modified 27-nt dsRNAs with dramatically enhanced stability in serum and long-term RNAi activity. Oligonucleotides 17, 445-464.
50. KUBO, T., ZHELEV, Z., OHBA, H., and BAKALOVA, R. (2008). Chemically modified symmetric and asymmetric duplex RNAs: an enhanced stability to nuclease degradation and gene silencing effect. Biochem. Biophys. Res. Commun. 365, 54-61.
51. LARA, M.F., GONZALEZ-GONZALEZ, E., SPEAKER, T.J., HICKERSON, R.P., LEAKE, D., MILSTONE, L.M., et al. (2012). Inhibition of CD44 gene expression in human skin models using self-delivery siRNA administered by dissolvable microneedle arrays. Hum. Gene Ther. doi:10.1089/hum.2011.211.
52. LAYZER, J.M., MCCAFFREY, A.P., TANNER, A.K., HUANG, Z.A.N., KAY, M.A. and SULLENGER, B.A. (2004). In vivo activity of nuclease-resistant siRNAs. RNA 10, 766-771.
53. LEACHMAN, S.A., HICKERSON, R.P., SCHWARTZ, M.E., BULLOUGH, E.E., HUTCHERSON, S.L., BOUCHER, K.M., et al. (2010). First-in-human mutation-targeted siRNA phase Ib trial of an inherited skin disorder. Mol. Ther. 18, 442-446.
54. LU, P.Y., and WOODLE, M.C. (2008). Delivering small interfering RNA for novel therapeutics. Methods Mol. Biol. 437, 93-107.
55. LUNDBERG, P., YANG, H.J., JUNG, S.J., BEHLKE, M.A., ROSE, S.D., and CANTIN, E.M. (2011). Protection against TNFalpha-dependent liver toxicity by intraperitoneal liposome delivered DsiRNA targeting TNFalpha in vivo. J. Control Release http://dx.doi.org/10.1016/j.jconrel.2011.10.034.
56. MATRANGA, C., TOMARI, Y., SHIN, C., BARTEL, D.P., and ZAMORE, P. D. (2005). Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123, 607-620.
57. MOSCHOS, S.A., WILLIAMS, A.E., and LINDSAY, M.A. (2007). Cell-penetrating-peptide-mediated siRNA lung delivery. Biochem. Soc. Trans. 35, 807-810.
58. OCAMPO, S.M., ROMERO, C., AVINO, A., BURGUENO, J., GASSULL, M.A., BERMUDEZ, J., et al. (2012). Functionally enhanced siRNA targeting TNFalpha attenuates DSS-induced colitis and TLR-mediated immunostimulation in mice. Mol. Ther. 20, 382-390.
59. PETRI, S., DUECK, A., LEHMANN, G., PUTZ, N., RUDEL, S., KREMMER, E., et al. (2011). Increased siRNA duplex stability correlates with reduced off-target and elevated on-target effects. RNA 17, 737-749.
60. POECK, H., BESCH, R., MAIHOEFER, C., RENN, M., TORMO, D., MORSKAYA, S. S., et al. (2008). 5′-Triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. Nat. Med. 14, 1256-63.
61. REYNOLDS, A., LEAKE, D., BOESE, Q., SCARINGE, S., MARSHALL, W.S., and KHVOROVA, A. (2004). Rational siRNA design for RNA interference. Nat. Biotechnol. 22, 326-330.
62. ROSE, S.D., KIM, D.H., AMARZGUIOUI, M., HEIDEL, J.D., COLLINGWOOD, M.A., DAVIS, M.E., et al. (2005). Functional polarity is introduced by Dicer processing of short substrate RNAs. Nucleic Acids Res. 33, 4140-4156.
63. SANO, M., SIERANT, M., MIYAGISHI, M., NAKANISHI, M., TAKAGI, Y., and SUTOU, S. (2008). Effect of asymmetric terminal structures of short RNA duplexes on the RNA interference activity and strand selection. Nucleic Acids Res. 36, 5812-5821.
64. SANTEL, A., ALEKU, M., KEIL, O., ENDRUSCHAT, J., ESCHE, V., DURIEUX, B., et al. (2006a). RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy. Gene Ther. 13, 1360-1370.
65. SANTEL, A., ALEKU, M., KEIL, O., ENDRUSCHAT, J., ESCHE, V., FISCH, G., et al. (2006b). A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene Ther. 13, 1222-1234.
66. SANTEL, A., ALEKU, M., RODER, N., MOPERT, K., DURIEUX, B., JANKE, O., et al. (2010). Atu027 prevents pulmonary metastasis in experimental and spontaneous mouse metastasis models. Clin. Cancer Res. 16, 5469-5480.
67. SCHWARZ, D.S., HUTVAGNER, G., DU, T., XU, Z., ARONIN, N., and ZAMORE, P. D. (2003). Asymmetry in the assembly of the RNAi enzyme complex. Cell 115, 199-208.
68. SEMPLE, S.C., AKINC, A., CHEN, J., SANDHU, A.P., MUI, B.L., CHO, C.K., et al. (2010). Rational design of cationic lipids for siRNA delivery. Nat. Biotechnol. 28, 172-176.
69. SIERANT, M., KAZMIERCZAK-BARANSKA, J., PADUSZYNSKA, A., SOBCZAK, M., PIETKIEWICZ, A., and NAWROT, B. (2010). Longer 19-base pair short interfering RNA duplexes rather than shorter duplexes trigger RNA interference. Oligonucleotides. 20, 199-206.
70. SIOLAS, D., LERNER, C., BURCHARD, J., GE, W., LINSLEY, P. S., PADDISON, P. J., et al. (2005). Synthetic shRNAs as potent RNAi triggers. Nat. Biotechnol. 23, 227-31.
71. SOUTSCHEK, J., AKINC, A., BRAMLAGE, B., CHARISSE, K., CONSTIEN, R., DONOGHUE, M., et al. (2004). Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432, 173-178.
72. STRUMBERG, D., SCHULTHEIS, B., TRAUGOTT, U., VANK, C., SANTEL, A., KEIL, O., et al. (2012). Phase I clinical development of Atu027, a siRNA formulation targeting PKN3 in patients with advanced solid tumors. Int. J. Clin. Pharmacol. Ther. 50, 76-8.
73. SUN, X., ROGOFF, H.A., and LI, C.J. (2008). Asymmetric RNA duplexes mediate RNA interference in mammalian cells. Nat. Biotechnol. 26, 1379-1782.
74. UI-TEI, K., NAITO, Y., ZENNO, S., NISHI, K., YAMATO, K., TAKAHASHI, F., et al. (2008). 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, 2136-2151.
75. VAISH, N., CHEN, F., SETH, S., FOSNAUGH, K., LIU, Y., ADAMI, R., et al. (2011). Improved specificity of gene silencing by siRNAs containing unlocked nucleobase analogs. Nucleic Acids Res. 39, 1823-1832.
76. WEITZER, S., and MARTINEZ, J. (2007). The human RNA kinase hClp1 is active on 3′ transfer RNA exons and short interfering RNAs. Nature 447, 222-226.
77. WOLFRUM, C., SHI, S., JAYAPRAKASH, K.N., JAYARAMAN, M., WANG, G., PANDEY, R.K., et al. (2007). Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat. Biotechnol. 25, 1149-1157.