Student or educator? Sign up with your school email and get 6 months of Pro free.
Cited by 2,027

The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.

Advances in oligonucleotide drug delivery

Roberts, Thomas C., Langer, Robert, Wood, Matthew J. A.·2020·Nature Reviews Drug Discovery

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41573-020-0075-7

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 37 references

Research works printed but not linked: 263

  1. Kim, J. et al. Patient-customized oligonucleotide therapy for a rare genetic disease. N. Engl. J. Med. 381, 1644–1652 (2019). This is the first study to utilize an oligonucleotide therapy tailored to a single patient. · DOI
  2. Giorgio, E. et al. Allele-specific silencing as treatment for gene duplication disorders: proof-of-principle in autosomal dominant leukodystrophy. Brain 142, 1905–1920 (2019). · DOI
  3. Southwell, A. L. et al. In vivo evaluation of candidate allele-specific mutant huntingtin gene silencing antisense oligonucleotides. Mol. Ther. 22, 2093–2106 (2014). · DOI
  4. Miller, V. M. et al. Allele-specific silencing of dominant disease genes. Proc. Natl Acad. Sci. USA 100, 7195–7200 (2003). · DOI
  5. Klein, A. F. et al. Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice. J. Clin. Invest. 129, 4739–4744 (2019). · DOI
  6. Crnković-Mertens, I., Semzow, J., Hoppe-Seyler, F. & Butz, K. Isoform-specific silencing of the Livin gene by RNA interference defines Livin β as key mediator of apoptosis inhibition in HeLa cells. J. Mol. Med. 84, 232–240 (2006). · DOI
  7. Valencia-Serna, J. et al. siRNA-mediated BCR–ABL silencing in primary chronic myeloid leukemia cells using lipopolymers. J. Controlled Rel. 310, 141–154 (2019). · DOI
  8. Wu, S. Y., Lopez-Berestein, G., Calin, G. A. & Sood, A. K. RNAi therapies: drugging the undruggable. Sci. Transl. Med. 6, 240ps7 (2014).
  9. Tushir-Singh, J. Antibody–siRNA conjugates: drugging the undruggable for anti-leukemic therapy. Expert Opin. Biol. Ther. 17, 325–338 (2017). · DOI
  10. Bobbin, M. L., Burnett, J. C. & Rossi, J. J. RNA interference approaches for treatment of HIV-1 infection. Genome Med. 7, 50 (2015). · DOI
  11. Hermann, T. & Patel, D. J. Adaptive recognition by nucleic acid aptamers. Science 287, 820–825 (2000). · DOI · Paper page
  12. Jackson, A. L. et al. Widespread siRNA ‘off-target’ transcript silencing mediated by seed region sequence complementarity. RNA 12, 1179–1187 (2006). · DOI
  13. Scacheri, P. C. et al. Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells. Proc. Natl Acad. Sci. USA 101, 1892–1897 (2004). · DOI
  14. Persengiev, S. P., Zhu, X. & Green, M. R. Nonspecific, concentration-dependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs). RNA 10, 12–18 (2004). · DOI
  15. Doench, J. G., Petersen, C. P. & Sharp, P. A. siRNAs can function as miRNAs. Genes Dev. 17, 438–442 (2003). · DOI
  16. Wu, H. et al. Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugs. J. Biol. Chem. 279, 17181–17189 (2004). · DOI
  17. Crooke, S. T. Molecular mechanisms of antisense oligonucleotides. Nucleic Acid. Ther. 27, 70–77 (2017). · DOI
  18. Monia, B. P. et al. Evaluation of 2′-modified oligonucleotides containing 2′-deoxy gaps as antisense inhibitors of gene expression. J. Biol. Chem. 268, 14514–14522 (1993). · DOI
  19. Liang, X.-H., Sun, H., Nichols, J. G. & Crooke, S. T. RNase H1-dependent antisense oligonucleotides are robustly active in directing RNA cleavage in both the cytoplasm and the nucleus. Mol. Ther. 25, 2075–2092 (2017). · DOI
  20. Lennox, K. A. & Behlke, M. A. Cellular localization of long non-coding RNAs affects silencing by RNAi more than by antisense oligonucleotides. Nucleic Acids Res. 44, 863–877 (2016). · DOI
  21. Dominski, Z. & Kole, R. Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides. Proc. Natl Acad. Sci. USA 90, 8673–8677 (1993). · DOI
  22. Singh, R. N. & Singh, N. N. Mechanism of splicing regulation of spinal muscular atrophy genes. Adv. Neurobiol. 20, 31–61 (2018). · DOI
  23. Aartsma-Rus, A. et al. Development of exon skipping therapies for Duchenne muscular dystrophy: a critical review and a perspective on the outstanding issues. Nucleic Acid. Ther. 27, 251–259 (2017). · DOI
  24. Wan, L. & Dreyfuss, G. Splicing-correcting therapy for SMA. Cell 170, 5 (2017). · DOI
  25. Ward, A. J., Norrbom, M., Chun, S., Bennett, C. F. & Rigo, F. Nonsense-mediated decay as a terminating mechanism for antisense oligonucleotides. Nucleic Acids Res. 42, 5871–5879 (2014). · DOI
  26. Boiziau, C. et al. Inhibition of translation initiation by antisense oligonucleotides via an RNase-H independent mechanism. Nucleic Acids Res. 19, 1113–1119 (1991). · DOI
  27. Baker, B. F. et al. 2′-O-(2-methoxy)ethyl-modified anti-intercellular adhesion molecule 1 (ICAM-1) oligonucleotides selectively increase the ICAM-1 mRNA level and inhibit formation of the ICAM-1 translation initiation complex in human umbilical vein endothelial cells. J. Biol. Chem. 272, 11994–12000 (1997). · DOI
  28. Liang, X.-H. et al. Translation efficiency of mRNAs is increased by antisense oligonucleotides targeting upstream open reading frames. Nat. Biotechnol. 34, 875–880 (2016). · DOI
  29. Nomakuchi, T. T., Rigo, F., Aznarez, I. & Krainer, A. R. Antisense oligonucleotide-directed inhibition of nonsense-mediated mRNA decay. Nat. Biotechnol. 34, 164–166 (2016). · DOI
  30. Vickers, T. A., Wyatt, J. R., Burckin, T., Bennett, C. F. & Freier, S. M. Fully modified 2′ MOE oligonucleotides redirect polyadenylation. Nucleic Acids Res. 29, 1293–1299 (2001). · DOI
  31. Elbashir, S. M. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498 (2001). · DOI · Paper page
  32. Liu, J. et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305, 1437–1441 (2004). · DOI · Paper page
  33. Roberts, T. C. The microRNA machinery. Adv. Exp. Med. Biol. 887, 15–30 (2015). · DOI
  34. Schürmann, N., Trabuco, L. G., Bender, C., Russell, R. B. & Grimm, D. Molecular dissection of human Argonaute proteins by DNA shuffling. Nat. Struct. Mol. Biol. 20, 818–826 (2013). · DOI
  35. Kim, D.-H. et al. Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nat. Biotechnol. 23, 222–226 (2005). · DOI
  36. Bramsen, J. B. et al. Improved silencing properties using small internally segmented interfering RNAs. Nucleic Acids Res. 35, 5886–5897 (2007). · DOI
  37. Byrne, M. et al. Novel hydrophobically modified asymmetric RNAi compounds (sd-rxRNA) demonstrate robust efficacy in the eye. J. Ocul. Pharmacol. Ther. 29, 855–864 (2013). · DOI
  38. Yu, D. et al. Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression. Cell 150, 895–908 (2012). · DOI
  39. Lima, W. F. et al. Single-stranded siRNAs activate RNAi in animals. Cell 150, 883–894 (2012). · DOI
  40. Svoronos, A. A., Engelman, D. M. & Slack, F. J. OncomiR or tumor suppressor? The duplicity of microRNAs in cancer. Cancer Res. 76, 3666–3670 (2016). · DOI
  41. Okada, N. et al. A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression. Genes Dev. 28, 438–450 (2014). · DOI
  42. Bueno, M. J. & Malumbres, M. MicroRNAs and the cell cycle. Biochim. Biophys. Acta 1812, 592–601 (2011). · DOI
  43. Shimakami, T. et al. Stabilization of hepatitis C virus RNA by an Ago2–miR-122 complex. Proc. Natl Acad. Sci. USA 109, 941–946 (2012). · DOI
  44. Balasubramaniam, M., Pandhare, J. & Dash, C. Are microRNAs important players in HIV-1 infection? An update. Viruses 10, 110 (2018). · DOI
  45. Xu, S. J., Hu, H. T., Li, H. L. & Chang, S. The role of miRNAs in immune cell development, immune cell activation, and tumor immunity: with a focus on macrophages and natural killer cells. Cells 8, 1140 (2019). · DOI
  46. Wendt, A., Esguerra, J. L. & Eliasson, L. Islet microRNAs in health and type-2 diabetes. Curr. Opin. Pharmacol. 43, 46–52 (2018). · DOI
  47. Vienberg, S., Geiger, J., Madsen, S. & Dalgaard, L. T. MicroRNAs in metabolism. Acta Physiol. 219, 346–361 (2017). · DOI
  48. van Rooij, E., Liu, N. & Olson, E. N. MicroRNAs flex their muscles. Trends Genet. 24, 159–166 (2008). · DOI
  49. Chen, J.-F. et al. microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7. J. Cell Biol. 190, 867–879 (2010). · DOI
  50. Roberts, T. C. et al. Expression analysis in multiple muscle groups and serum reveals complexity in the microRNA transcriptome of the MDX mouse with implications for therapy. Mol. Ther. Nucleic Acids 1, e39 (2012).
  51. Cacchiarelli, D. et al. MicroRNAs involved in molecular circuitries relevant for the Duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway. Cell Metab. 12, 341–351 (2010). · DOI
  52. Provost, P. et al. Ribonuclease activity and RNA binding of recombinant human Dicer. EMBO J. 21, 5864–5874 (2002). · DOI
  53. Lee, Y. et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415–419 (2003). · DOI
  54. Filipowicz, W., Bhattacharyya, S. N. & Sonenberg, N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat. Rev. Genet. 9, 102–114 (2008). · DOI
  55. Roberts, T. C. & Wood, M. J. A. Therapeutic targeting of non-coding RNAs. Essays Biochem. 54, 127–145 (2013). · DOI
  56. Lindow, M. & Kauppinen, S. Discovering the first microRNA-targeted drug. J. Cell Biol. 199, 407–412 (2012). · DOI
  57. Jopling, C. L., Yi, M., Lancaster, A. M., Lemon, S. M. & Sarnow, P. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 309, 1577–1581 (2005). · DOI
  58. Jopling, C. L., Schütz, S. & Sarnow, P. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe 4, 77–85 (2008). · DOI
  59. Jopling, C. L. Targeting microRNA-122 to treat hepatitis C virus infection. Viruses 2, 1382–1393 (2010). · DOI
  60. Janssen, H. L. A. et al. Treatment of HCV infection by targeting microRNA. N. Engl. J. Med. 368, 1685–1694 (2013). · DOI
  61. Machlin, E. S., Sarnow, P. & Sagan, S. M. Masking the 5′ terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA–target RNA complex. Proc. Natl Acad. Sci. USA 108, 3193–3198 (2011). · DOI
  62. Ottosen, S. et al. In vitro antiviral activity and preclinical and clinical resistance profile of miravirsen, a novel anti-hepatitis C virus therapeutic targeting the human factor miR-122. Antimicrob. Agents Chemother. 59, 599–608 (2015). · DOI
  63. Gomez, I. G. et al. Anti-microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways. J. Clin. Invest. 125, 141–156 (2015). · DOI
  64. Seto, A. G. et al. Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma. Br. J. Haematol. 183, 428–444 (2018). · DOI
  65. Gallant-Behm, C. L. et al. A microRNA-29 mimic (remlarsen) represses extracellular matrix expression and fibroplasia in the skin. J. Invest. Dermatol. 139, 1073–1081 (2019). · DOI
  66. Choi, W.-Y., Giraldez, A. J. & Schier, A. F. Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science 318, 271–274 (2007). · DOI
  67. Wang, Z. The principles of miRNA-masking antisense oligonucleotides technology. Methods Mol. Biol. 676, 43–49 (2011). · DOI
  68. Roberts, T. C., Morris, K. V. & Wood, M. J. A. The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369, (2014). · DOI
  69. Wahlestedt, C. Targeting long non-coding RNA to therapeutically upregulate gene expression. Nat. Rev. Drug Discov. 12, 433–446 (2013). · DOI
  70. Yoon, S. & Rossi, J. J. Therapeutic potential of small activating RNAs (saRNAs) in human cancers. Curr. Pharm. Biotechnol. 19, 604–610 (2018). · DOI
  71. Modarresi, F. et al. Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nat. Biotechnol. 30, 453–459 (2012). · DOI
  72. Meng, L. et al. Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Nature 518, 409–412 (2015). · DOI
  73. Hsiao, J. et al. Upregulation of haploinsufficient gene expression in the brain by targeting a long non-coding RNA improves seizure phenotype in a model of Dravet syndrome. EBioMedicine 9, 257–277 (2016). · DOI
  74. Schwartz, J. C. et al. Antisense transcripts are targets for activating small RNAs. Nat. Struct. Mol. Biol. 15, 842–848 (2008). · DOI
  75. Matsui, M. et al. Promoter RNA links transcriptional regulation of inflammatory pathway genes. Nucleic Acids Res. 41, 10086–10109 (2013). · DOI
  76. Turunen, T. A. et al. Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress. Sci. Rep. 9, 10332 (2019).
  77. Gagnon, K. T., Li, L., Chu, Y., Janowski, B. A. & Corey, D. R. RNAi factors are present and active in human cell nuclei. Cell Rep. 6, 211–221 (2014). · DOI · Paper page
  78. Voutila, J. et al. Development and mechanism of small activating RNA targeting CEBPA, a novel therapeutic in clinical trials for liver cancer. Mol. Ther. 25, 2705–2714 (2017). · DOI
  79. Reebye, V. et al. Gene activation of CEBPA using saRNA: preclinical studies of the first in human saRNA drug candidate for liver cancer. Oncogene 37, 3216–3228 (2018). · DOI
  80. Sarker, D. et al. MTL-CEBPA, a small activating RNA therapeutic up-regulating C/EBP-α, in patients with advanced liver cancer: a first-in-human, multi-centre, open-label, phase I trial. Clin. Cancer Res. https://doi.org/10.1158/1078-0432.CCR-20-0414 (2020). This paper presents the currently most advanced oligonucleotide therapy aimed at upregulating a target gene. · DOI
  81. Tsui, N. B. Y., Ng, E. K. O. & Lo, Y. M. D. Stability of endogenous and added RNA in blood specimens, serum, and plasma. Clin. Chem. 48, 1647–1653 (2002). · DOI
  82. Iversen, F. et al. Optimized siRNA–PEG conjugates for extended blood circulation and reduced urine excretion in mice. Theranostics 3, 201–209 (2013). · DOI
  83. Geary, R. S., Norris, D., Yu, R. & Bennett, C. F. Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides. Adv. Drug Deliv. Rev. 87, 46–51 (2015). · DOI
  84. Shemesh, C. S. et al. Pharmacokinetic and pharmacodynamic investigations of ION-353382, a model antisense oligonucleotide: using α2-macroglobulin and murinoglobulin double-knockout mice. Nucleic Acid. Ther. 26, 223–235 (2016). · DOI
  85. Allen, T. M. The use of glycolipids and hydrophilic polymers in avoiding rapid uptake of liposomes by the mononuclear phagocyte system. Adv. Drug Delivery Rev. 13, 285–309 (1994). · DOI
  86. Sahay, G. et al. Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat. Biotechnol. 31, 653–658 (2013). · DOI · Paper page
  87. Finkel, R. S. et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet 388, 3017–3026 (2016). This landmark study shows efficacy of an oligonucleotide therapy for spinal muscular atrophy. · DOI
  88. Wan, W. B. & Seth, P. P. The medicinal chemistry of therapeutic oligonucleotides. J. Med. Chem. 59, 9645–9667 (2016). · DOI
  89. Hung, G. et al. Characterization of target mRNA reduction through in situ RNA hybridization in multiple organ systems following systemic antisense treatment in animals. Nucleic Acid. Ther. 23, 369–378 (2013). · DOI
  90. Hall, A. H. S., Wan, J., Shaughnessy, E. E., Ramsay Shaw, B. & Alexander, K. A. RNA interference using boranophosphate siRNAs: structure–activity relationships. Nucleic Acids Res. 32, 5991–6000 (2004). · DOI
  91. Braasch, D. A. et al. RNA interference in mammalian cells by chemically-modified RNA. Biochemistry 42, 7967–7975 (2003). · DOI
  92. Bijsterbosch, M. K. et al. In vivo fate of phosphorothioate antisense oligodeoxynucleotides: predominant uptake by scavenger receptors on endothelial liver cells. Nucleic Acids Res. 25, 3290–3296 (1997). · DOI
  93. Ezzat, K. et al. Self-assembly into nanoparticles is essential for receptor mediated uptake of therapeutic antisense oligonucleotides. Nano Lett. 15, 4364–4373 (2015). · DOI
  94. Miller, C. M. et al. Stabilin-1 and Stabilin-2 are specific receptors for the cellular internalization of phosphorothioate-modified antisense oligonucleotides (ASOs) in the liver. Nucleic Acids Res. 44, 2782–2794 (2016). · DOI
  95. Gaus, H. J. et al. Characterization of the interactions of chemically-modified therapeutic nucleic acids with plasma proteins using a fluorescence polarization assay. Nucleic Acids Res. 47, 1110–1122 (2019). · DOI
  96. Brown, D. A. et al. Effect of phosphorothioate modification of oligodeoxynucleotides on specific protein binding. J. Biol. Chem. 269, 26801–26805 (1994). · DOI
  97. Liang, X., Sun, H., Shen, W. & Crooke, S. T. Identification and characterization of intracellular proteins that bind oligonucleotides with phosphorothioate linkages. Nucleic Acids Res. 43, 2927–2945 (2015). · DOI
  98. Weidner, D. A., Valdez, B. C., Henning, D., Greenberg, S. & Busch, H. Phosphorothioate oligonucleotides bind in a non sequence-specific manner to the nucleolar protein C23/nucleolin. FEBS Lett. 366, 146–150 (1995). · DOI
  99. Shen, W., Liang, X. & Crooke, S. T. Phosphorothioate oligonucleotides can displace NEAT1 RNA and form nuclear paraspeckle-like structures. Nucleic Acids Res. 42, 8648–8662 (2014). · DOI
  100. Liang, X., Shen, W., Sun, H., Prakash, T. P. & Crooke, S. T. TCP1 complex proteins interact with phosphorothioate oligonucleotides and can co-localize in oligonucleotide-induced nuclear bodies in mammalian cells. Nucleic Acids Res. 42, 7819–7832 (2014). · DOI
  101. Monia, B. P., Johnston, J. F., Sasmor, H. & Cummins, L. L. Nuclease resistance and antisense activity of modified oligonucleotides targeted to Ha-ras. J. Biol. Chem. 271, 14533–14540 (1996). · DOI
  102. Iwamoto, N. et al. Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides. Nat. Biotechnol. 35, 845–851 (2017). This study demonstrates the influence of phosphorothioate stereochemistry on the properties of gapmer ASOs. · DOI
  103. Wan, W. B. et al. Synthesis, biophysical properties and biological activity of second generation antisense oligonucleotides containing chiral phosphorothioate linkages. Nucleic Acids Res. 42, 13456–13468 (2014). · DOI
  104. Lee, H.-S. et al. Abasic pivot substitution harnesses target specificity of RNA interference. Nat. Commun. 6, 10154 (2015).
  105. Liu, J. et al. RNA duplexes with abasic substitutions are potent and allele-selective inhibitors of huntingtin and ataxin-3 expression. Nucleic Acids Res. 41, 8788–8801 (2013). · DOI
  106. Schirle, N. T. & MacRae, I. J. The crystal structure of human Argonaute2. Science 336, 1037–1040 (2012). · DOI
  107. Frank, F., Sonenberg, N. & Nagar, B. Structural basis for 5′-nucleotide base-specific recognition of guide RNA by human AGO2. Nature 465, 818–822 (2010). · DOI · Paper page
  108. Haraszti, R. A. et al. 5′-Vinylphosphonate improves tissue accumulation and efficacy of conjugated siRNAs in vivo. Nucleic Acids Res. 45, 7581–7592 (2017). · DOI
  109. Behlke, M. A. Chemical modification of siRNAs for in vivo use. Oligonucleotides 18, 305–319 (2008). · DOI
  110. Southwell, A. L., Skotte, N. H., Bennett, C. F. & Hayden, M. R. Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases. Trends Mol. Med. 18, 634–643 (2012). · DOI
  111. Manoharan, M. 2′-Carbohydrate modifications in antisense oligonucleotide therapy: importance of conformation, configuration and conjugation. Biochim. Biophys. Acta 1489, 117–130 (1999). · DOI
  112. Roberts, T. C., Ezzat, K., El Andaloussi, S. & Weinberg, M. S. Synthetic siRNA delivery: progress and prospects. Methods Mol. Biol. 1364, 291–310 (2016). · DOI
  113. Prakash, T. P. et al. Positional effect of chemical modifications on short interference RNA activity in mammalian cells. J. Med. Chem. 48, 4247–4253 (2005). · DOI
  114. Allerson, C. R. et al. Fully 2′-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA. J. Med. Chem. 48, 901–904 (2005). · DOI
  115. Hassler, M. R. et al. Comparison of partially and fully chemically-modified siRNA in conjugate-mediated delivery in vivo. Nucleic Acids Res. 46, 2185–2196 (2018). · DOI · Paper page
  116. Jackson, A. L. et al. Position-specific chemical modification of siRNAs reduces ‘off-target’ transcript silencing. RNA 12, 1197–1205 (2006). · DOI
  117. Garber, K. Alnylam terminates revusiran program, stock plunges. Nat. Biotechnol. 34, 1213–1214 (2016). · DOI
  118. Nair, J. K. et al. Impact of enhanced metabolic stability on pharmacokinetics and pharmacodynamics of GalNAc–siRNA conjugates. Nucleic Acids Res. 45, 10969–10977 (2017). · DOI · Paper page
  119. Judge, A. D. et al. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat. Biotechnol. 23, 457–462 (2005). · DOI
  120. Shen, W., Liang, X.-H., Sun, H. & Crooke, S. T. 2′-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation of P54nrb and PSF. Nucleic Acids Res. 43, 4569–4578 (2015). · DOI
  121. Iwasaki, A. & Medzhitov, R. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5, 987–995 (2004). · DOI
  122. Hornung, V. et al. Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med. 11, 263–270 (2005). · DOI
  123. Morrissey, D. V. et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat. Biotechnol. 23, 1002–1007 (2005). This landmark study demonstrates enhanced RNAi-mediated gene silencing using chemically modified siRNA in vivo. · DOI
  124. Judge, A. D., Bola, G., Lee, A. C. H. & MacLachlan, I. Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol. Ther. 13, 494–505 (2006). · DOI
  125. Poeck, H. et al. 5′-Triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. Nat. Med. 14, 1256–1263 (2008). · DOI · Paper page
  126. Kortylewski, M. et al. In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nat. Biotechnol. 27, 925–932 (2009). · DOI
  127. Kandimalla, E. R. et al. Design, synthesis and biological evaluation of novel antagonist compounds of Toll-like receptors 7, 8 and 9. Nucleic Acids Res. 41, 3947–3961 (2013). · DOI
  128. Veedu, R. N. & Wengel, J. Locked nucleic acid as a novel class of therapeutic agents. RNA Biol. 6, 321–323 (2009). · DOI
  129. Morita, K. et al. 2′-O,4′-C-ethylene-bridged nucleic acids (ENA): highly nuclease-resistant and thermodynamically stable oligonucleotides for antisense drug. Bioorg. Med. Chem. Lett. 12, 73–76 (2002). · DOI
  130. Koshkin, A. A. et al. LNA (locked nucleic acids): synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition. Tetrahedron 54, 3607–3630 (1998). · DOI
  131. Obad, S. et al. Silencing of microRNA families by seed-targeting tiny LNAs. Nat. Genet. 43, 371–378 (2011). · DOI
  132. Moulton, J. D. Using morpholinos to control gene expression. Curr. Protoc. Nucleic Acid. Chem. 68, 4.30.1–4.30.29 (2017). · DOI
  133. Iversen, P. L. Phosphorodiamidate morpholino oligomers: favorable properties for sequence-specific gene inactivation. Curr. Opin. Mol. Ther. 3, 235–238 (2001).
  134. Komaki, H. et al. Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. Sci. Transl Med. 10, eaan0713 (2018). · DOI
  135. Larsen, H. J., Bentin, T. & Nielsen, P. E. Antisense properties of peptide nucleic acid. Biochim. Biophys. Acta 1489, 159–166 (1999). · DOI
  136. Saarbach, J., Sabale, P. M. & Winssinger, N. Peptide nucleic acid (PNA) and its applications in chemical biology, diagnostics, and therapeutics. Curr. Opin. Chem. Biol. 52, 112–124 (2019). · DOI
  137. Renneberg, D. & Leumann, C. J. Watson–Crick base-pairing properties of tricyclo-DNA. J. Am. Chem. Soc. 124, 5993–6002 (2002). · DOI
  138. Goyenvalle, A. et al. Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers. Nat. Med. 21, 270–275 (2015). · DOI
  139. Dowling, J. J. Eteplirsen therapy for Duchenne muscular dystrophy: skipping to the front of the line. Nat. Rev. Neurol. 12, 675–676 (2016). · DOI
  140. Yin, H. et al. Optimization of peptide nucleic acid antisense oligonucleotides for local and systemic dystrophin splice correction in the MDX mouse. Mol. Ther. 18, 819–827 (2010). · DOI
  141. Imbert, M., Blandel, F., Leumann, C., Garcia, L. & Goyenvalle, A. Lowering mutant huntingtin using tricyclo-DNA antisense oligonucleotides as a therapeutic approach for Huntington’s disease. Nucleic Acid. Ther. 29, 256–265 (2019). · DOI
  142. Meade, B. R. et al. Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications. Nat. Biotechnol. 32, 1256–1261 (2014). · DOI
  143. Wolfrum, C. et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat. Biotechnol. 25, 1149–1157 (2007). · DOI · Paper page
  144. Soutschek, J. et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432, 173–178 (2004). · DOI
  145. Lorenz, C., Hadwiger, P., John, M., Vornlocher, H.-P. & Unverzagt, C. Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells. Bioorg. Med. Chem. Lett. 14, 4975–4977 (2004). · DOI
  146. Eguchi, A. et al. Efficient siRNA delivery into primary cells by a peptide transduction domain–dsRNA binding domain fusion protein. Nat. Biotechnol. 27, 567–571 (2009). · DOI
  147. Betts, C. et al. Pip6–PMO, a new generation of peptide–oligonucleotide conjugates with improved cardiac exon skipping activity for DMD treatment. Mol. Ther. Nucleic Acids 1, e38 (2012). · DOI
  148. Alam, Md. R. et al. Multivalent cyclic RGD conjugates for targeted delivery of small interfering RNA. Bioconjugate Chem. 22, 1673–1681 (2011). · DOI
  149. Ämmälä, C. et al. Targeted deliivery of antisense oligonucleotides to pancreatic β-cells. Sci. Adv. 4, eaat3386 (2018). · DOI
  150. Liu, X. et al. Tumor-targeted in vivo gene silencing via systemic delivery of cRGD-conjugated siRNA. Nucleic Acids Res. 42, 11805–11817 (2014). · DOI
  151. McNamara, J. O. et al. Cell type-specific delivery of siRNAs with aptamer–siRNA chimeras. Nat. Biotechnol. 24, 1005–1015 (2006). · DOI
  152. Song, E. et al. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat. Biotechnol. 23, 709–717 (2005). This paper demonstrates antibody–siRNA conjugates for gene silencing in mice. · DOI
  153. Matsuda, S. et al. siRNA conjugates carrying sequentially assembled trivalent N-acetylgalactosamine linked through nucleosides elicit robust gene silencing in vivo in hepatocytes. ACS Chem. Biol. 10, 1181–1187 (2015). · DOI
  154. Tai, W. Current aspects of siRNA bioconjugate for in vitro and in vivo delivery. Molecules 24, 2211 (2019). · DOI
  155. Juliano, R. L. The delivery of therapeutic oligonucleotides. Nucleic Acids Res. 44, 6518–6548 (2016). · DOI
  156. Khan, T. et al. Silencing myostatin using cholesterol-conjugated siRNAs induces muscle growth. Mol. Ther. Nucleic Acids 5, e342 (2016). · DOI
  157. Nishina, K. et al. Efficient in vivo delivery of siRNA to the liver by conjugation of α-tocopherol. Mol. Ther. 16, 734–740 (2008). · DOI
  158. Osborn, M. F. et al. Hydrophobicity drives the systemic distribution of lipid-conjugated siRNAs via lipid transport pathways. Nucleic Acids Res. 47, 1070–1081 (2019). · DOI
  159. Spiess, M. The asialoglycoprotein receptor: a model for endocytic transport receptors. Biochemistry 29, 10009–10018 (1990). · DOI
  160. Tanowitz, M. et al. Asialoglycoprotein receptor 1 mediates productive uptake of N-acetylgalactosamine-conjugated and unconjugated phosphorothioate antisense oligonucleotides into liver hepatocytes. Nucleic Acids Res. 45, 12388–12400 (2017). · DOI
  161. Prakash, T. P. et al. Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice. Nucleic Acids Res. 42, 8796–8807 (2014). · DOI
  162. Zimmermann, T. S. et al. Clinical proof of concept for a novel hepatocyte-targeting GalNAc–siRNA conjugate. Mol. Ther. 25, 71–78 (2017). · DOI
  163. Sardh, E. et al. Phase 1 trial of an RNA interference therapy for acute intermittent porphyria. N. Engl. J. Med. 380, 549–558 (2019). · DOI
  164. Hooper, A. J. & Burnett, J. R. Anti-PCSK9 therapies for the treatment of hypercholesterolemia. Expert Opin. Biol. Ther. 13, 429–435 (2013). · DOI
  165. Mousavi, S. A., Berge, K. E. & Leren, T. P. The unique role of proprotein convertase subtilisin/kexin 9 in cholesterol homeostasis. J. Intern. Med. 266, 507–519 (2009). · DOI
  166. Sievers, E. L. & Senter, P. D. Antibody–drug conjugates in cancer therapy. Annu. Rev. Med. 64, 15–29 (2013). · DOI
  167. Yao, Y. et al. Targeted delivery of PLK1–siRNA by ScFv suppresses Her2+ breast cancer growth and metastasis. Sci. Transl Med. 4, 130ra48 (2012).
  168. Kumar, P. et al. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 134, 577–586 (2008). · DOI
  169. Sugo, T. et al. Development of antibody–siRNA conjugate targeted to cardiac and skeletal muscles. J. Control. Rel. 237, 1–13 (2016). · DOI
  170. Cuellar, T. L. et al. Systematic evaluation of antibody-mediated siRNA delivery using an industrial platform of THIOMAB–siRNA conjugates. Nucleic Acids Res. 43, 1189–1203 (2015). · DOI
  171. Arnold, A. E. et al. Antibody–antisense oligonucleotide conjugate downregulates a key gene in glioblastoma stem cells. Mol. Ther. Nucleic Acids 11, 518–527 (2018). · DOI
  172. Astriab-Fisher, A., Fisher, M. H., Juliano, R. & Herdewijn, P. Increased uptake of antisense oligonucleotides by delivery as double stranded complexes. Biochem. Pharmacol. 68, 403–407 (2004). · DOI
  173. Nuzzo, S. et al. Potential and challenges of aptamers as specific carriers of therapeutic oligonucleotides for precision medicine in cancer. Cancers 11, 1521 (2019). · DOI
  174. Hong, S., Sun, N., Liu, M., Wang, J. & Pei, R. Building a chimera of aptamer–antisense oligonucleotide for silencing galectin-1 gene. RSC Adv. 6, 112445–112450 (2016). · DOI
  175. White, R. R., Sullenger, B. A. & Rusconi, C. P. Developing aptamers into therapeutics. J. Clin. Invest. 106, 929–934 (2000). · DOI
  176. McClorey, G. & Banerjee, S. Cell-penetrating peptides to enhance delivery of oligonucleotide-based therapeutics. Biomedicines 6, 51 (2018). · DOI
  177. Yin H. et al. Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. Hum. Mol. Genet. 17, 3909–3918 (2008). · DOI
  178. McClorey, G., Moulton, H. M., Iversen, P. L., Fletcher, S. & Wilton, S. D. Antisense oligonucleotide-induced exon skipping restores dystrophin expression in vitro in a canine model of DMD. Gene Ther. 13, 1373–1381 (2006). · DOI
  179. Wu, B. et al. Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer. Proc. Natl Acad. Sci. USA 105, 14814–14819 (2008). · DOI
  180. Abes, R. et al. Delivery of steric block morpholino oligomers by (R-X-R)4 peptides: structure–activity studies. Nucleic Acids Res. 36, 6343–6354 (2008). · DOI
  181. Wender, P. A. et al. The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: peptoid molecular transporters. Proc. Natl Acad. Sci. USA 97, 13003–13008 (2000). · DOI
  182. Yin, H. et al. A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice. Hum. Mol. Genet. 18, 4405–4414 (2009). · DOI
  183. Yin, H. et al. Context dependent effects of chimeric peptide morpholino conjugates contribute to dystrophin exon-skipping efficiency. Mol. Ther. Nucleic Acids 2, e124 (2013).
  184. Gao, X. et al. Effective dystrophin restoration by a novel muscle-homing peptide–morpholino conjugate in dystrophin-deficient MDX mice. Mol. Ther. 22, 1333–1341 (2014). · DOI
  185. Yin, H. et al. Pip5 transduction peptides direct high efficiency oligonucleotide-mediated dystrophin exon skipping in heart and phenotypic correction in MDX mice. Mol. Ther. 19, 1295–1303 (2011). · DOI
  186. van Westering, T. L. E. et al. Uniform sarcolemmal dystrophin expression is required to prevent extracellular microRNA release and improve dystrophic pathology. J. Cachexia Sarcopenia Muscle 11, 578–593 (2019). · DOI
  187. Gait, M. J. et al. Cell-penetrating peptide conjugates of steric blocking oligonucleotides as therapeutics for neuromuscular diseases from a historical perspective to current prospects of treatment. Nucleic Acid. Ther. 29, 1–12 (2019). · DOI
  188. Betts, C. A. et al. Prevention of exercised induced cardiomyopathy following Pip–PMO treatment in dystrophic mdx mice. Sci. Rep. 5, 8986 (2015).
  189. Hammond, S. M. et al. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy. Proc. Natl Acad. Sci. USA 113, 10962–10967 (2016). · DOI
  190. Amantana, A. et al. Pharmacokinetics, biodistribution, stability and toxicity of a cell-penetrating peptide–morpholino oligomer conjugate. Bioconjug. Chem. 18, 1325–1331 (2007). · DOI
  191. Moulton, H. M. & Moulton, J. D. Morpholinos and their peptide conjugates: therapeutic promise and challenge for Duchenne muscular dystrophy. Biochim. Biophys. Acta 1798, 2296–2303 (2010). · DOI
  192. Lehto, T. et al. Cellular trafficking determines the exon skipping activity of Pip6a–PMO in MDX skeletal and cardiac muscle cells. Nucleic Acids Res. 42, 3207–3217 (2014). · DOI
  193. Abes, S. 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. Rel. 116, 304–313 (2006). · DOI
  194. Bestas, B. et al. Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model. J. Clin. Invest. 124, 4067–4081 (2014). · DOI
  195. Du, L. et al. Arginine-rich cell-penetrating peptide dramatically enhances AMO-mediated ATM aberrant splicing correction and enables delivery to brain and cerebellum. Hum. Mol. Genet. 20, 3151–3160 (2011). · DOI
  196. Geller, B. L. et al. Gene-silencing antisense oligomers inhibit acinetobacter growth in vitro and in vivo. J. Infect. Dis. 208, 1553–1560 (2013). · DOI
  197. Burrer, R. et al. Antiviral effects of antisense morpholino oligomers in murine coronavirus infection models. J. Virol. 81, 5637–5648 (2007). · DOI
  198. Neuman, B. W. et al. Inhibition and escape of SARS-CoV treated with antisense morpholino oligomers. Adv. Exp. Med. Biol. 581, 567–571 (2006). · DOI
  199. Enterlein, S. et al. VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice. Antimicrob. Agents Chemother. 50, 984–993 (2006). · DOI
  200. Moschos, S. A. et al. Lung delivery studies using siRNA conjugated to TAT(48–60) and penetratin reveal peptide induced reduction in gene expression and induction of innate immunity. Bioconjug. Chem. 18, 1450–1459 (2007). · DOI

200 of 263 shown

Cited by

See all 2,027

Metadata

Authors
Roberts, T. C., Langer, R., & Wood, M. J. A.
Venue
Nature Reviews Drug Discovery
Published
2020-08-11
Volume
19
Issue
10
Pages
673-694
ISSN
  • 1474-1776
  • 1474-1784
Cited by
2,027
References
37
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Advances in oligonucleotide drug delivery. https://app.cochat.ai/papers/10.1038/s41573-020-0075-7
The paper
Roberts, T. C., Langer, R., & Wood, M. J. A. (2020). Advances in oligonucleotide drug delivery. Nature Reviews Drug Discovery. https://doi.org/10.1038/s41573-020-0075-7

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.