Abstract
This introduction charts the history of the development of the major chemical modifications that have influenced the development of nucleic acids therapeutics focusing in particular on antisense oligonucleotide analogues carrying modifications in the backbone and sugar. Brief mention is made of siRNA development and other applications that have by and large utilized the same modifications. We also point out the pitfalls of the use of nucleic acids as drugs, such as their unwanted interactions with pattern recognition receptors, which can be mitigated by chemical modification or used as immunotherapeutic agents.
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References
- Zamecnik PC, Stephenson ML. Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc Natl Acad Sci U S A. 1978;75:280–284. doi: 10.1073/pnas.75.1.280. [DOI] [PMC free article] [PubMed]
- De Clercq E, Eckstein F, Merigan TC. Interferon induction increased through chemical modification of a synthetic polynucleotide. Science. 1969;165:1137–1139. doi: 10.1126/science.165.3898.1137. [DOI] [PubMed]
- Agrawal S, Gait MJ, editors. Advances in nucleic acid therapeutics. Royal Society of Chemistry; London: 2019. (Drug discovery series).
- Sekiya T, Takeya T, Brown EL, Belagaje R, Contreras R, Fritz H-J, Gait MJ, Lees RG, Ryan MJ, Khorana HG, Norris KE. Total synthesis of a tyrosine suppressor tRNA gene (16). Enzymatic joings to form the total 208 base-pair long DNA. J Biol Chem. 1979;254:5787–5801. [PubMed]
- Letsinger RL, Mahadevan V. Oligonucletiode synthesis on a polymer support. J Am Chem Soc. 1965;87:3526–3527. doi: 10.1021/ja01093a058. [DOI] [PubMed]
- Gait MJ, Sheppard RC. A polyamide support for oligonucleotide synthesis. J Am Chem Soc. 1976;98:8514–8516.
- Gait MJ, Singh M, Sheppard RC, Edge M, Greene AR, Heathcliffe GR, Atkinson TC, Newton CR, Markham AF. Rapid synthesis of oligodeoxyribonucleotides IV. Improved solid phase synthesis of oligodeoxyribonucleotides through phosphotriester intermediates. Nucl Acids Res. 1980;8:1080–1096. doi: 10.1093/nar/8.5.1081. [DOI] [PMC free article] [PubMed]
- Sproat BS, Gait MJ. In: Oligonucleotide synthesis: a practical approach. Gait MJ, editor. IRL Press; Oxford: 1984. Solid-phase synthesis of oligodeoxyribonucleotides by the phosphotriester method; pp. 83–114.
- Miyoshi K, Itakura K. Solid phase synthesis of nonadecathymidylic acids by the phosphotriester method. Tetrahedron Lett. 1979;20:3635–3638.
- Beaucage SL, Caruthers MH. Deoxynucleoside phosphoramidites-A new class of key intermediates for deoxypolynucleotide synthesis. Tetrahedron Lett. 1981;22:1859–1862.
- Reese CB. The chemical synthesis of oligo- and poly-nucleoties: a personal commentary. Tetrahedron. 2002;58:8893–8920.
- Reese CB. Oligo- and polynucleotides: 50 years of chemical synthesis. Org Biomol Chem. 2005;3:3851–3868. doi: 10.1039/b510458k. [DOI] [PubMed]
- Barker RH, Jr, Metelev V, Rapaport E, Zamec-nik P. Inhibition of Plasmodium falciparum malaria using antisense oligodeoxynucleotides. Proc Natl Acad Sci USA. 1996;93(1):514–518. doi: 10.1073/pnas.93.1.514. [DOI] [PMC free article] [PubMed]
- Zamecnik PC, Goodchild J, Taguchi Y, Sarin PS. Inhibition of replication and expression of human T-cell lymphotropic virus type III in cultured cells by exogenous synthetic oligonucleotides complementary to viral RNA. Proc Natl Acad Sci U S A. 1986;83(12):4143–4146. doi: 10.1073/pnas.83.12.4143. [DOI] [PMC free article] [PubMed]
- Stec WJ, Zon G, Egan W, Stec B. Automated solid-phase synthesis, separation, and stereochemistry of Phosphorothioate analogues of oligodeoxyribonucleotides. J Am Chem Soc. 1984;106:6077–6079.
- Agrawal S, Goodchild J, Civeira MP, Thornton AH, Sarin PS, Zamecnik PC. Oligodeoxynucleoside phosphoramidates and phosphorothioates as inhibitors of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1988;85(19):7079–7083. doi: 10.1073/pnas.85.19.7079. [DOI] [PMC free article] [PubMed]
- Matsukura M, Shinozuka K, Zon G, Mitsuya H, Reitz M, Cohen J, Broder S. Phosphorothioate analogs of oligodeoxyribonucleotides: inhibitors of replication and cytopathic effects of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1987;84:7706–7710. doi: 10.1073/pnas.84.21.7706. [DOI] [PMC free article] [PubMed]
- Agrawal S, Ikeuchi T, Sun D, Sarin PS, Konopka A, Maizel J, Zamecnik PC. Inhibition of human immunodeficiency virus in early infected and chronically infected cells by antisense oligodeoxynucleotides and their phosphorothioate analogues. Proc Natl Acad Sci U S A. 1989;86:7790–7794. doi: 10.1073/pnas.86.20.7790. [DOI] [PMC free article] [PubMed]
- Agrawal S, Mayrand SH, Zamecnik PC, Pederson T. Site-specific excision from RNA by RNase H and mixed-phosphate-backbone oligodeoxynucleotides. Proc Natl Acad Sci U S A. 1990;87(4):1401–1405. doi: 10.1073/pnas.87.4.1401. [DOI] [PMC free article] [PubMed]
- Walder RY, Walder JA. Role of RNase H in hybrid-arrested translation by antisense oligonucleotides. Proc Natl Acad Sci U S A. 1988;85(14):5011–5015. doi: 10.1073/pnas.85.14.5011. [DOI] [PMC free article] [PubMed]
- Leiter JM, Agrawal S, Palese P, Zamecnik PC. Inhibition of influenza virus replication by phosphorothioate oligodeoxynucleotides. Proc Natl Acad Sci U S A. 1990;87(9):3430–3434. doi: 10.1073/pnas.87.9.3430. [DOI] [PMC free article] [PubMed]
- Gaudette MF, Hampikian G, Metelev V, Agrawal S, Crain WR. Effect on embryos of injection of phosphorothioate-modified oligonucleotides into pregnant mice. Antisense Res Dev. 1993;3:391–397. doi: 10.1089/ard.1993.3.391. [DOI] [PubMed]
- Knorre DG, Vlassov VV. Reactive oligonucleotide derivatives as gene-targeted biologically active compounds and affinity probes. Genetica. 1991;85:53–63. doi: 10.1007/BF00056106. [DOI] [PubMed]
- Ratajczak MZ, Kant JA, Luger SM, Hijiya N, Zhang J, Zon G, Gewirtz AM. In vivo treatment of human leukemia in a scid mouse model with c-myb antisense oligodeoxynucleotides. Proc Natl Acad Sci U S A. 1992;89(24):11823–11827. doi: 10.1073/pnas.89.24.11823. [DOI] [PMC free article] [PubMed]
- Cowsert LM, Fox MC, Zon G, Mirabelli CK. In vitro evaluation of phosphorothioate oligonucleotides targeted to the E2 mRNA of papillomavirus: potential treatment for genital warts. Antimicrob Agents Chemother. 1993;37(2):171–177. doi: 10.1128/aac.37.2.171. [DOI] [PMC free article] [PubMed]
- Flores-Aguilar M, Freeman WR, Wiley CA, Gangan P, Munguia D, Tatebayashi M, Vuong C, Besen G. Evaluation of retinal toxicity and efficacy of anticytomegalovirus and anti-herpes simplex virus antiviral phosphorothioate oligonucleotides ISIS 2922 and ISIS 4015. J Infect Dis. 1997;175:1308–1316. doi: 10.1086/516461. [DOI] [PubMed]
- Monia BP, Johnston JF, Geiger T, Muller M, Fabbro D. Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase. Nat Med. 1996;2(6):668–675. doi: 10.1038/nm0696-668. [DOI] [PubMed]
- Dean NM, McKay R. Inhibition of protein kinase C-alpha expression in mice after systemic administration of phosphorothioate antisense oligodeoxynucleotides. Proc Natl Acad Sci U S A. 1994;91(24):11762–11766. doi: 10.1073/pnas.91.24.11762. [DOI] [PMC free article] [PubMed]
- Agrawal S. Antisense oligonucleotides as antiviral agents. Trends Biotechnol. 1992;10(5):152–158. doi: 10.1016/0167-7799(92)90203-8. [DOI] [PubMed]
- Monia BP, Lesnik EA, Gonzalez C, Lima WF, McGee D, Guinosso CJ, Kawasaki AM, Cook PD, Freier SM. Evaluation of 2′-modified oligonucleotides containing 2′-deoxy gaps as antisense inhibitors of gene expression. J Biol Chem. 1993;268:14514–14522. [PubMed]
- Agrawal S, Temsamani J, Tang JY. Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. Proc Natl Acad Sci U S A. 1991;88(17):7595–7599. doi: 10.1073/pnas.88.17.7595. [DOI] [PMC free article] [PubMed]
- Temsamani J, Roskey A, Chaix C, Agrawal S. In vivo metabolic profile of a phosphorothioate oligodeoxyribonucleotide. Antis Nucl Acid Drug Dev. 1997;7(3):159–165. doi: 10.1089/oli.1.1997.7.159. doi: 10.1089/oli.1.1997.7.159. [DOI] [PubMed]
- Temsamani J, Tang JY, Padmapriya A, Kubert M, Agrawal S. Pharmacokinetics, biodistribution, and stability of capped oligodeoxynucleotide phosphorothioates in mice. Antisense Res Dev. 1993;3(3):277–284. doi: 10.1089/ard.1993.3.277. [DOI] [PubMed]
- Agrawal S, Temsamani J, Galbraith W, Tang J. Pharmacokinetics of antisense oligonucleotides. Clin Pharmacokinet. 1995;28(1):7–16. doi: 10.2165/00003088-199528010-00002. doi: 10.2165/00003088-199528010-00002. [DOI] [PubMed]
- Agrawal S, Zhang X, Cai Q, Kandimalla ER, Manning A, Jiang Z, Marcel T, Zhang R. Effect of aspirin on protein binding and tissue disposition of oligonucleotide phosphorothioate in rats. J Drug Target. 1998;5(4):303–312. doi: 10.3109/10611869808995883. doi: 10.3109/10611869808995883. [DOI] [PubMed]
- Dean N, McKay R, Miraglia L, Howard R, Cooper S, Giddings J, Nicklin P, Meister L, Ziel R, Geiger T, Muller M, et al. Inhibition of growth of human tumor cell lines in nude mice by an antisense of oligonucleotide inhibitor of protein kinase C-alpha expression. Cancer Res. 1996;56(15):3499–3507. [PubMed]
- Moriya K, Matsukura M, Kurokawa K, Koike K. In vivo inhibition of hepatitis B virus gene expression by antisense phosphorothioate oligonucleotides. Biochem Biophys Res Commun. 1996;218(1):217–223. doi: 10.1006/bbrc.1996.0038.S0006-291X(96)90038-8. doi: 10.1006/bbrc.1996.0038.S0006-291X(96)90038-8. [DOI] [PubMed]
- Gura T. Antisense has growing pains. Science. 1995;270(5236):575–577. doi: 10.1126/science.270.5236.575. [DOI] [PubMed]
- Lewis EJ, Agrawal S, Bishop J, Chadwick J, Cristensen ND, Cuthill S, Dunford P, Field AK, Francis J, Gibson V, Greenham AK, et al. Non-specific antiviral activity of antisense molecules targeted to the E1 region of human papillomavirus. Antivir Res. 2000;48(3):187–196.:S0166354200001297 [pii] doi: 10.1016/s0166-3542(00)00129-7. [DOI] [PubMed]
- Agrawal S, Iyer RP. Perspectives in antisense therapeutics. Pharmacol Therapeut. 1997;76:151–160. doi: 10.1016/s0163-7258(97)00108-3. [DOI] [PubMed]
- Levin AA. A review of the issues in the pharmacokinetics and toxicology of phosphorothioate antisense oligonucleotides. Biochim Biophys Acta. 1999;1489(1):69–84.:S0167-4781(99)00140-2 [pii] doi: 10.1016/s0167-4781(99)00140-2. [DOI] [PubMed]
- Galbraith WM, Hobson WC, Giclas PC, Schechter PJ, Agrawal S. Complement activation and hemodynamic changes following intravenous administration of phosphorothioate oligonucleotides in the monkey. Antisense Res Dev. 1994;4(3):201–206. doi: 10.1089/ard.1994.4.201. [DOI] [PubMed]
- Black LE, Farrelly JG, Cavagnaro JA, Ahn CH, DeGeorge JJ, Taylor AS, DeFelice AF, Jordan A. Regulatory considerations for oligonucleotide drugs: updated recommendations for pharmacology and toxicology studies. Antisense Res Dev. 1994;4(4):299–301. doi: 10.1089/ard.1994.4.299. [DOI] [PubMed]
- Agrawal S. [Accessed 9 Dec 2020];United States Securities and Exchange Commission report. 2001 https://www.sec.gov/Archives/edgar/data/861838/000095013501501616/b39654hye8-k.txt .
- Bayever E, Iversen PL, Bishop MR, Sharp JG, Tewary HK, Arneson MA, Pirruccello SJ, Ruddon RW, Kessinger A, Zon G, et al. Systemic administration of a phosphorothioate oligonucleotide with a sequence complementary to p53 for acute myelogenous leukemia and myelodysplastic syndrome: initial results of a phase I trial. Antisense Res Dev. 1993;3(4):383–390. doi: 10.1089/ard.1993.3.383. [DOI] [PubMed]
- de Smet MD, Meenken CJ, van den Horn GJ. Fomivirsen - a phosphorothioate oligonucleotide for the treatment of CMV retinitis. Ocul Immunol Inflamm. 1999;7(3-4):189–198. doi: 10.1076/ocii.7.3.189.4007. [DOI] [PubMed]
- Nemunaitis J, Holmlund JT, Kraynak M, Richards D, Bruce J, Ognoskie N, Kwoh TJ, Geary R, Dorr A, Von Hoff D, Eckhardt SG. Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C-alpha, in patients with advanced cancer. J Clin Oncol. 1999;17(11):3586–3595. doi: 10.1200/JCO.1999.17.11.3586. doi: 10.1200/JCO.1999.17.11.3586. [DOI] [PubMed]
- Grindel JM, Musick TJ, Jiang Z, Roskey A, Agrawal S. Pharmacokinetics and metabolism of an oligodeoxynucleotide phosphorothioate (GEM 91) in cynomologous monkeys following intravenous infusion. Antis Nucl Acid Drug Dev. 1998;8:43–52. doi: 10.1089/oli.1.1998.8.43. [DOI] [PubMed]
- Sereni D, Tubiana R, Lascoux C, Katlama C, Taulera O, Bourque A, Cohen A, Dvorchik B, Martin RR, Tournerie C, Gouyette A, et al. Pharmacokinetics and tolerability of intravenous trecovirsen (GEM 91), an antisense phosphorothioate oligonucleotide, in HIV-positive subjects. J Clin Pharmacol. 1999;39(1):47–54. doi: 10.1177/00912709922007552. [DOI] [PubMed]
- Agrawal S. Antisense oligonucleotides: towards clinical trials. Trends Biotechnol. 1996;14(10):376–387. doi: 10.1016/0167-7799(96)10053-6.0167-7799(96)10053-6. doi: 10.1016/0167-7799(96)10053-6.0167-7799(96)10053-6. [DOI] [PubMed]
- Agrawal S, Kandimalla ER. Role of Toll-like receptors in antisense and siRNA [corrected] Nat Biotechnol. 2004;22(12):1533–1537. doi: 10.1038/nbt1042.nbt1042. doi: 10.1038/nbt1042.nbt1042. [DOI] [PubMed]
- Krieg AM, Yi A-K, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretsky GA, Klinman DM. CpG motife in bacterial DNA trigger direct B-cell activation. Nature. 1995;374:546–549. doi: 10.1038/374546a0. [DOI] [PubMed]
- Messina JP, Gilkeson GS, Pisetsky DS. Stimulation of in vitro murine lymphocyte proliferation by bacterial DNA. J Immunol. 1991;147:1759–1764. [PubMed]
- Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S. A Tolllike receptor recognizes bacterial DNA. Nature. 2000;408(6813):740–745. doi: 10.1038/35047123. doi: 10.1038/35047123. [DOI] [PubMed]
- Agrawal S, Martin RR. Was induction of HIV-1 through TLR9? J Immunol. 2003;171(4):1621. author reply 1621-1622. doi: 10.4049/jimmunol.171.4.1621. [DOI] [PubMed]
- Agrawal S. Importance of nucleotide sequence and chemical modifications of antisense oligonucleotides. Biochim Biophys Acta. 1999;1489:53–68. doi: 10.1016/s0167-4781(99)00141-4. [DOI] [PubMed]
- Agrawal S, Kandimalla ER. Antisense therapeutics: is it as simple as complementary base recognition? Mol Med Today. 2000;6(2):72–81.:S1357-4310(99)01638-X [pii] doi: 10.1016/s1357-4310(99)01638-x. [DOI] [PubMed]
- Eckstein F. Nucleoside phosphorothioates. Annu Rev Biochem. 1985;54:367–402. doi: 10.1146/annurev.bi.54.070185.002055. [DOI] [PubMed]
- Kurpiewski MR, Koziolkiewicz M, Wilk A, Stec WJ, Jen-Jacobson L. Chiral phos-phorothioates as probes of protein interactions with individual DNA phosphoryl oxygens: essential interactions of EcoRI endonuclease with the phosphate at pGAATTC. Biochemistry. 1996;35(27):8846–8854. doi: 10.1021/bi960261e.bi960261e. doi: 10.1021/bi960261e.bi960261e. [DOI] [PubMed]
- Guo M, Yu D, Iyer RP, Agrawal S. Solid-phase stereoselective synthesis of 2′-O-methyl-oligoribonucleoside phosphorothioates using nucleoside bicyclic oxazaphospholidines. Bioorg Med Chem Lett. 1998;8:2539–2544. doi: 10.1016/s0960-894x(98)00450-8. [DOI] [PubMed]
- Yu D, Kandimalla ER, Roskey A, Zhao Q, Chen L, Chen J, Agrawal S. Stereoenriched phosphorothioate oligodeoxynucleotides: synthesis, biophysical and biological properties. Bioorg Med Chem. 2000;8(1):275–284.:S0968-0896(99)00275-8 [pii] doi: 10.1016/s0968-0896(99)00275-8. [DOI] [PubMed]
- Iwamoto N, Butler DCD, Svrzikapa N, Mohapatra S, Zlatev I, Sah DWY, Meena Standley SM, Lu G, Apponi LH, Frank-Kamenetsky M, Zhang JJ, et al. Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides. Nat Biotechnol. 2017;35(9):845–851. doi: 10.1038/nbt.3948.nbt.3948. doi: 10.1038/nbt.3948.nbt.3948. [DOI] [PubMed]
- Østergaard ME, De Hoyos CL, Wan WB, Shen W, Low A, Berdeja A, Vasquez G, Murray S, Migawa MT, Liang X-H, Swayze EE, et al. Understanding the effect of controlling phosphorothioate chirality in the DNA gap on the potency and safety of gapmer antisense oligonucleotides. Nucl Acids Res. 2020;48:1691. doi: 10.1093/nar/gkaa031. doi: 10.1093/nar/gkaa031. [DOI] [PMC free article] [PubMed]
- Wave Life Sciences Press Release. [Accessed 9 Dec 2020];Wave Life Sciences announces discontinuation of Suvodirsen development for Duchenne Muscular Dystrophy. 2019 https://ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-announces-discontinuation-suvodirsen .
- Wave Life Sciences Press Release. [Accessed 9 Dec 2020];Wave Life Sciences announces Suvodirsen Phase 1 safety and tolerability data and Phase 2/3 Clinical Trial design. 2019 https://ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-announces-suvodirsen-phase-1-safety-and .
- Miller PS, Agris CH, Murakami A, Reddy PM, Spitz SA, Ts’o POP. Preparation of oligodeoxyribonudeoside methylphosphonates on a polystyrene support. Nucl Acids Res. 1983;11:6225–6241. doi: 10.1093/nar/11.18.6225. [DOI] [PMC free article] [PubMed]
- Asai A, Oshima Y, Yamamoto Y, Uochi T, Kusaka H, Akinaga S, Yamashita Y, Pongracz K, Pruzan R, Wunder E, Piatyszek M, et al. A novel telomerase template antagonist (GRN163) as a potential anticancer agent. Cancer Res. 2003;63:3931–3939. [PubMed]
- Agrawal S, Goodchild J. Oligodeoxynucleoside methylphosphonates: synthesis and enzymic degradation. Tetrahedron Lett. 1987;28:3539–3542.
- Summerton J, Weller D. Uncharged Morpholino-based polymers having phosphorus containing chiral intersubunit linkages. 1993
- Summerton J. Morpholino antisense oligomers: the case for an RNase H-independent structural type. Biochim Biophys Acta. 1999;1489:141–158. doi: 10.1016/s0167-4781(99)00150-5. [DOI] [PubMed]
- Enterlein S, Warfield KL, Swenson DL, Stein DA, Smith JL, Gamble CS, Kroeker AD, Iversen PL, Bavari S, Mühlberger E. VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice. Antimicrob Agents Chemother. 2006;50:984–993. doi: 10.1128/AAC.50.3.984-993.2006. [DOI] [PMC free article] [PubMed]
- Kinali M, Arechavala-Gomeza V, Feng L, Cirak S, Hunt D, Adkin C, Guglieri M, Ashton E, Abbs S, Nihoyanopoulos P, Garraldi EM, et al. Restoration of dystrophin expression in Duchenne muscular dystrophy: a single blind placebo-controlled dose escalation study using morpholino oligomer AVI-4658. Lancet. 2009;8:918. doi: 10.1016/S1474-4422(09)70211-X. [DOI] [PMC free article] [PubMed]
- Aartsma-Rus A, Arechavala-Gomeza V. Why dystrophin quantification is key in the eteplirsen saga. Nat Rev Neurol. 2018;14:454–456. doi: 10.1038/s41582-018-0033-8. [DOI] [PubMed]
- Jäarver P, O’Donovan L, Gait MJ. A chemical view of oligonucleotides for exon skipping and related drug applications. Nucl Acids Ther. 2014;24:37–47. doi: 10.1089/nat.2013.0454. [DOI] [PMC free article] [PubMed]
- Egholm M, Buchardt O, Nielsen PE, Berg RH. Peptide Nucleic Acids (PNA). Oligonucleotide analogues with an achiral backbone. J Am Chem Soc. 1992;114:1895–1897.
- Rapozzi V, Burm BE, Cogioi S, van der Marel GA, van Boom JH, Quadrifoglio F, Xodo LE. Anti-proliferative effect in chronic myeloid leukaemia cells by antisense peptide nucleic acids. Nucl Acids Res. 2002;30:3712–3721. doi: 10.1093/nar/gkf451. [DOI] [PMC free article] [PubMed]
- Villa R, Folini M, Lualdi S, Veronese S, Daidone MG, Zaffaroni N. Inhibition of telomerase activity by a cell-penetrating peptide nucleic acid construct in human melanoma cells. FEBS Lett. 2000;473:241–248. doi: 10.1016/s0014-5793(00)01540-4. [DOI] [PubMed]
- Chaubey B, Tripathi S, Ganguly S, Harris D, Casale RA, Pandey VN. A PNA-Transportan conjugate targeted to the TAR region of the HIV-1 genome exhibits both antiviral and virucidal properties. Virology. 2005;331:418–428. doi: 10.1016/j.virol.2004.10.032. [DOI] [PubMed]
- Chaubey B, Tripathi S, Pandey VN. Single acute-dose and repeat-doses toxicity anti-HIV-1 PNATAR-Penetratin conjugates after intraperitoneal administration to mice. Oligonucleotides. 2008;18:9–20. doi: 10.1089/oli.2007.0088. [DOI] [PubMed]
- Good L, Awasthi SK, Dryselius R, Larsson O, Nielsen PE. Bactericidal antisense effects of peptide-PNA conjugates. Nat Biotech. 2001;19:360–364. doi: 10.1038/86753. [DOI] [PubMed]
- Good L, Nielsen PE. Inhibition of translation and bacterial cell growth by peptide nucleic acid targeted to ribosomal RNA. Proc Natl Acad Sci U S A. 1998;95:2073–2076. doi: 10.1073/pnas.95.5.2073. [DOI] [PMC free article] [PubMed]
- Torres AG, Fabani MM, Vigorito E, Williams D, Al-Obaidi N, Wojcechowski F, Hudosn RHE, Seitz O, Gait MJ. Chemical structure requirements and cellular targeting of microRNA-122 by peptide nucleic acids anti-miRs. Nucl Acids Res. 2012;40:2152–2167. doi: 10.1093/nar/gkr885. [DOI] [PMC free article] [PubMed]
- Inoue H, Hayase Y, Iwai S, Ohtsuka E. Sequence-dependent hydrolysis of RNA using modified oligonucleotide splints and RNase H. Nucl Acids Symp Ser. 1987;18:221–224. [PubMed]
- Yu D, Iyer RP, Shaw DR, Lisziewicz J, Li Y, Jiang Z, Roskey A, Agrawal S. Hybrid oligonucleotides: synthesis, biophysical properties, stability studies, and biological activity. Bioorg Med Chem. 1996;4(10):1685–1692.:0968089696001605 [pii] doi: 10.1016/0968-0896(96)00160-5. [DOI] [PubMed]
- Metelev V, Lisziewicz J, Agrawal S. Study of antisense oligonucleotide phosphorothioates containing segments of oligodeoxynucleotides and 2′-o-methylribonucleotides. Bioorg Med Chem Lett. 1994;4:2929–2934.
- Agrawal S, Jiang Z, Zhao Q, Shaw D, Cal Q, Roskey A, Channavajjala L, Saxinger C, Zhang R. Mixed-backbone oligonucleotidesas second generation antisense oligonucleotides: in vitro and in vivo studies. Proc Natl Acad Sci U S A. 1997;94:2620–2625. doi: 10.1073/pnas.94.6.2620. [DOI] [PMC free article] [PubMed]
- Zhou W, Agrawal S. Mixed-backbone oligonucleotides as second-generation antisense agents with reduced phosphorothioate-related side effects. Bioorg Med Chem Lett. 1998;8:3269–3274. doi: 10.1016/s0960-894x(98)00591-5. [DOI] [PubMed]
- Sierakowska H, Sambade MJ, Agrawal S, Kole R. Repair of thalassemic human betaglobin mRNA in mammalian cells by antisense oligonucleotides. Proc Natl Acad Sci U S A. 1996;93(23):12840–12844. doi: 10.1073/pnas.93.23.12840. [DOI] [PMC free article] [PubMed]
- Wilton SD, Lloyd F, Carville K, Fletcher S, Honeyman K, Agrawal S, Kole R. Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides. Neuromuscul Disord. 1999;9(5):330–338.:S0960896699000103 [pii] doi: 10.1016/s0960-8966(99)00010-3. [DOI] [PubMed]
- FDA Panel. FDA advisory panel votes BioMarin’s drisapersentrials not persuasive. 2015. [Accessed 9 Dec 2020]. https://www.fdanews.com/articles/174238-fda-advisory-panel-votes-biomarins-drisapersentrials-not-persuasive?v¼preview .
- Aartsma-Rus A. FDA approval of nusinersen for Spinal Muscular Atrophy makes 2016 the year of splice modulating oligonucleotides. Nucl Acids Ther. 2017;27:67–69. doi: 10.1089/nat.2017.0665. [DOI] [PubMed]
- Mercuri E, Darras BT, Chiriboga CA, Day JW, Campbell C, Connolly AM, Iannaccone ST, Kirschner J, Kuntz NL, Saito K, Shieh PB, et al. Nusinersen versus sham control in later-onset Spinal Muscular Atrophy. New Engl J Med. 2018;378:625–635. doi: 10.1056/NEJMoa1710504. [DOI] [PubMed]
- Arzumanov A, Walsh AP, Liu X, Rajwanshi VK, Wengel J, Gait MJ. Oligonucleotide analogue interference with the HIV-1 Tat protein-TAR RNA interaction. Nucleos Nucleot Nucl Acids. 2001;20:471–480. doi: 10.1081/NCN-100002321. [DOI] [PubMed]
- Lindow M, Kauppinen S. Discovering the first microRNA targeted drug. J Cell Biol. 2012;199:407–412. doi: 10.1083/jcb.201208082. [DOI] [PMC free article] [PubMed]
- Morita K, Hasegawa C, Kaneko M, Tsutsumi S, Sone J, Ishikawa T, Imanishi T, Koizumi M. 2′-O,4′-C-ethylene-bridged nucleic acids (ENA) with nuclease-resistance and high affinity for RNA. Nucl Acids Res. 2001;1(Suppl):241–242. doi: 10.1093/nass/1.1.241. [DOI] [PubMed]
- Lee T, Awano H, Yagi M, Matsumoto M, Watanabe N, Goda R, Koizumi M, Takeshima Y, Matsuo M. 2′-O-methyl RNA/ethylene-bridged nucleic acid chimera antisense oligonucleotides to induce dystrophin exon 45 skipping. Genes. 2017;8(2):67. doi: 10.3390/genes8020067.genes8020067. doi: 10.3390/genes8020067.genes8020067. [DOI] [PMC free article] [PubMed]
- Renneberg D, Leumann CJ. Watson-Crick base-pairing properties of tricyclo-DNA. J Am Chem Soc. 2002;124:5993–6004. doi: 10.1021/ja025569+. [DOI] [PubMed]
- Seth PP, Siwkowski A, Allerson CR, Vasquez G, Lee S, Prakash TP, Kinberger G, Migawa MT, Gaus H, Bhat B, Swayze EE. Design, synthesis and evaluation of constrained methoxyethyl (cMOE) and constrained ethyl (cEt) nucleoside analogs. Nucl Acids Symp Ser. 2008;52:553–554. doi: 10.1093/nass/nrn280.nrn280. doi: 10.1093/nass/nrn280.nrn280. [DOI] [PubMed]
- Flanagan WM, Wagner RW, Grant D, Lin K-Y, Matteucci M. Cellular penetration and antisense activity by a phenoxazine-substituted heptanucleotide. Nat Biotech. 1999;17:48–52. doi: 10.1038/5220. [DOI] [PubMed]
- Henry S, Stecker K, Brooks D, Monteith D, Conklin B, Bennett CF. Chemically modified oligonucleotides exhibit decreased immune stimulation in mice. J Pharmacol Exp Ther. 2000;292(2):468–479. [PubMed]
- Yu D, Wang D, Zhu FG, Bhagat L, Dai M, Kandimalla ER, Agrawal S. Modifications incorporated in CpG motifs of oligodeoxynucleotides lead to antagonist activity of toll-like receptors 7 and 9. J Med Chem. 2009;52(16):5108–5114. doi: 10.1021/jm900730r. doi: 10.1021/jm900730r. [DOI] [PubMed]
- Zhang R, Iyer RP, Yu D, Tan W, Zhang X, Lu Z, Zhao H, Agrawal S. Pharmacokinetics and tissue disposition of a chimeric oligodeoxynucleoside phosphorothioate in rats after intravenous administration. J Pharmacol Exp Ther. 1996;278(2):971–979. [PubMed]
- Kandimalla ER, Temsamani J, Agrawal S. Synthesis and properties of 2′-O-methylribonucleotide methylphosphonate containing chimeric oligonucleotides. Nucleos Nucleot. 2007;14:1031–1035.
- Agrawal S, Zhang X, Lu Z, Zhao H, Tamburin JM, Yan J, Cai H, Diasio RB, Habus I, Jiang Z, et al. Absorption, tissue distribution and in vivo stability in rats of a hybrid antisense oligonucleotide following oral administration. Biochem Pharmacol. 1995;50(4):571–576.:0006295295001602 [pii] doi: 10.1016/0006-2952(95)00160-2. [DOI] [PubMed]
- Shen LX, Kandimalla ER, Agrawal S. Impact of mixed-backbone oligonucleotides on target binding affinity and target cleaving specificity and selectivity by Escherichia coli RNase H. Bioorg Med Chem. 1998;6:1695–1705. doi: 10.1016/s0968-0896(98)00131-x. [DOI] [PubMed]
- Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Plant-é-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. New Engl J Med. 2018;379:22–31. doi: 10.1056/NEJMoa1716793. [DOI] [PMC free article] [PubMed]
- Witztum JL, Gaudet D, Freedman SD, Alexander VA, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, et al. Volanesorsen and triglyceride levels in Familial Chylomicronemia Syndrome. New Engl J Med. 2019;381:531–542. doi: 10.1056/NEJMoa1715944. [DOI] [PubMed]
- Reeskamp LF, Kastelein JJP, Moriarty PM, Duell PB, Catapano AL, Santos RD, Ballan-tyne CM. Safety and efficacy of mipomersen in patients with heterozygous familial hypercholesterolemia. Atherosclerosis. 2019;280:109–117. doi: 10.1016/j.atherosclerosis.2018.11.017. [DOI] [PubMed]
- Frieden M, Orum H. The application of locked nucleic acids in the treatment of cancer. IDrugs. 2006;9:706–711. [PubMed]
- Hong D, Kurzrock R, Kim Y, Woessner R, Younes A, Nemunaitis J, Fowler N, Zhou T, Schmidt J, Jo M, Lee SJ, et al. AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer. Sci Transl Med. 2015;7:314ra185 doi: 10.1126/scitranslmed.aac5272. [DOI] [PMC free article] [PubMed]
- Seth PP, Yu J, Jazayeri A, Pallan PS, Allerson CR, Østergaard ME, Liu F, Herdewijn P, Egli M, Swayze EE. Synthesis and antisense properties of Fluoro Cyclohexenyl Nucleic Acid (F-CeNA), a nuclease stable mimic of 2′-fluoro RNA. J Org Chem. 2012;77:5074–5085. doi: 10.1021/jo300594b. [DOI] [PMC free article] [PubMed]
- Allart B, Khan K, Rosemeyer H, Schepers G, Hendrix C, Rothenbacher K, Seela F, Van Aerschot A, Herdewijn P. D-Altritol Nucleic Acids (ANA): hybridisation properties, stability, and initial structural analysis. Chem Eur J. 1999;5:2424–2431.
- Carroll JB, Warby SC, Southwell AL, Doty CN, Greenlee S, Skotte N, Hung G, Bennett CF, Freier SM, Hayden MR. Potent and selective antisense oligonucleotides targeting single nucleotide polymorphisms in the Huntington Disease gene/allele-specific silencing of mutant Huntingtin. Mol Ther. 2011;19:2178–2185. doi: 10.1038/mt.2011.201. [DOI] [PMC free article] [PubMed]
- Kamola PJ, Kitson JDA, Turner G, Maratou K, Eriksson S, Panjwani A, Warnock LC, Douillard GA, Moores K, Koppe EL, Wixted WE, et al. In silico and in vitro evaluation of exonic and intronic off-target effects form a critical element of therapeutic ASO gapmer optimization. Nucl Acids Res. 2015;43:8638–8650. doi: 10.1093/nar/gkv857. [DOI] [PMC free article] [PubMed]
- Kasuya T, Hori S, Watanabe A, Nakajima M, Gahara Y, Rokushima M, Yanagimoto T, Kugimiya A. Ribonuclease H1-dependent hepatotoxicity caused by locked nucleic acid-modified gapmer antisense oligonucleotides. Sci Rep. 2016;6:30377. doi: 10.1038/srep30377. [DOI] [PMC free article] [PubMed]
- Burel SA, Hart CE, Cauntey P, Hsiao J, Machemer T, Katz M, Watt A, Bul HH, Younis H, Sabripour M, Freier SM, et al. Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts. Nucl Acids Res. 2016;44:2093–2109. doi: 10.1093/nar/gkv1210. [DOI] [PMC free article] [PubMed]
- Swayze EE, Siwkowski AM, Wancewicz EV, Migawa MT, Wyrzykiewicz TK, Hung G, Monia BP, Bennett CF. Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals. Nucl Acids Res. 2007;35:687–700. doi: 10.1093/nar/gkl1071. [DOI] [PMC free article] [PubMed]
- Ferrari N, Bergeron D, Tedeschi A-L, Mangos MM, Paquet L, Renzi PM, Damha MJ. Characterization of antisense oligonucleotides comprising 2′-deoxy-2′-fluoro-β-d-arabinonucleic acid (FANA) Ann N Y Acad Sci. 2006;1082:91–102. doi: 10.1196/annals.1348.032. [DOI] [PubMed]
- Egli M, Pallan PS, Allerson CR, Prakash TP, Berdeja A, Yu J, Lee S, Watt A, Gaus H, Bhat B, Swayze EE, et al. Synthesis, improved antisense activity and structural rationale for the divergent RNA affinities of 3′-fluoro hexitol nucleic acid (FHNA and Ara-FHNA) modified oligonucleotides. J Am Chem Soc. 2011;133:16642–16649. doi: 10.1021/ja207086x. [DOI] [PMC free article] [PubMed]
- Parmar R, Willoughby JLS, Liu J, Foster DJ, Brighham B, Theile CS, Charisse K, Akinc A, Guidry E, Pei Y, Strapps W, et al. 5′-(E)-Vinylphosphonate: a stable phosphate mimic can improve the RNAi activity of siRNA-GalNAc conjugates. Chem-BioChem. 2016;17:985–989. doi: 10.1002/cbic.201600130. [DOI] [PubMed]
- Godfrey C, Desviat LR, Smedsrød B, Piétri-Rouxel F, Denti MA, Disterer P, Lorain S, Nogales-Gadea G, Sardon V, Anwar R, El Andaloussi S, et al. Delivery is key: lessons learnt from developing splice-switching antisense therapies. EMBO Mol Med. 2017;9:545–557. doi: 10.15252/emmm.201607199. [DOI] [PMC free article] [PubMed]
- Ray KK, Landmesser U, Leiter LA, Kallend D, Dufour R, Karakas M, Hall T, Troquay RPT, Turner T, Visseren FLJ, Wijngard P, et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. New Engl J Med. 2017;376:1430–1440. doi: 10.1056/NEJMoa1615758. [DOI] [PubMed]
- Godhino BMDC, Coles AH, Khvorova A. In: Advances in nucleic acid therapeutics. Agrawal S, Gait MJ, editors. Royal Society of Chemistry; London: 2019. Conjugate-mediated delivery of RNAi-based therapeutics: enhancing pharmacokinetics-pharmacodynamics relationships of medicinal oligonucleotides; pp. 206–232.
- Killanthottathil GR, Manoharan M. In: Advances in nucleic acid therapeutics. Agrawal S, Gait MJ, editors. Royal Society of Chemistry; London: 2019. Liver-targeted RNAi therapeutics: principles and applications; pp. 233–265.
- Chirigos MA, Papademetriou V, Bartocci A, Read E, Levy HB. Immune response modifying activity in mice of polyinosinic: polycytidylic acid stabilized with poly-L-lysine, in carboxymethylcellulose [Poly-ICLC] Int J Immunopharmacol. 1981;3:329–337. doi: 10.1016/0192-0561(81)90028-x. [DOI] [PubMed]
- Pisetsky DS. Immune activation by bacterial DNA: a new genetic code. Immunity. 1996;5:303–310. doi: 10.1016/s1074-7613(00)80256-3. [DOI] [PubMed]
- Boller T, Felix G. A renaissance of elicitors: perception of microbe-associated molecular patterns and danger signals by pattern-recognition receptors. Annu Rev Plant Biol. 2009;60:379–406. doi: 10.1146/annurev.arplant.57.032905.105346. [DOI] [PubMed]
- Palm NW, Medzhitov R. Pattern recognition receptors and control of adaptive immunity. Immunol Rev. 2008;227:221–233. doi: 10.1111/j.1600-065X.2008.00731.x. [DOI] [PubMed]
- Blasius AL, Beutler B. Intracellular toll-like receptors. Immunity. 2011;32:305–315. doi: 10.1016/j.immuni.2010.03.012. [DOI] [PubMed]
- Kandimalla ER, Agrawal S. Toll and toll-like receptors: an immunologic perspective Molecular Biology Intelligence Unit. Springer; Boston, MA: 2005. Agonists of toll-like receptor 9; pp. 181–212.
- Bauer S, Kirschning CJ, H€acker H, Redecke V, Hausmann S, Akira S, Wagner H, Lipford GB. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci U S A. 2001;98:9237–9242. doi: 10.1073/pnas.161293498. [DOI] [PMC free article] [PubMed]
- Cho WG, Albuquerque RJC, Kleinman ME, Taralio V, Greco A, Nozaki M, Green MG, Baffi JZ, Ambati BK, De Falco M, Alexander JS, et al. Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth. Proc Natl Acad Sci U S A. 2009;106:7137–7142. doi: 10.1073/pnas.0812317106. [DOI] [PMC free article] [PubMed]
- Kleinman ME, Yamada K, Takeda A, Chandrasekaran V, Nozaki M, Baffi JZ, Albuquerque RJC, Yamasaki S, Itaya M, Pan Y, Appukuttan B, et al. Sequence-and target-independent angiogenesis suppression by siRNA via TLR3. Nature. 2008;452:591–597. doi: 10.1038/nature06765. [DOI] [PMC free article] [PubMed]
- Lan T, Wang D, Bhagat L, Philbin VJ, Yu D, Tang JX, Putta MR, Sullivan T, La Monica N, Kandimalla ER, Agrawal S. Design of synthetic oligoribonucleotide-based agonists of Toll-like receptor 3 and their immune response profiles in vitro and in vivo. Org Biomol Chem. 2013;11:1049–1058. doi: 10.1039/c2ob26946e. [DOI] [PubMed]
- Putta MR, Zhu FG, Wang D, Bhagat L, Kandimalla ER, Agrawal S. Peptide conjugation at the 5′-end of oligodeoxynucleotides abrogates Toll-Like Receptor 9-mediated immune stimulatory activity. Bioconjug Chem. 2010;21:39–45. doi: 10.1021/bc900425s. [DOI] [PubMed]
- Agrawal S, Kandimalla ER. Antisense and/or immunostimulatory oligonucleotide therapeutics. Curr Cancer Drug Targets. 2001;1(3):197–209. doi: 10.2174/1568009013334160. [DOI] [PubMed]
- Jackson S, Lenting J, Kopp J, Murray L, Ellison W, Rhee M, Shockey G, Akelia L, Ery K, Hayward WL, Janssen RS. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine. 2018;36:668–674. doi: 10.1016/j.vaccine.2017.12.038. [DOI] [PubMed]
- Guyadar D, Bogomolv P, Kobalava Z, Moiseev V, Szlavik J, Astruc B, Varkonyi L, Sullivan T. 1209 IMO-2025 plus Ribavirin gives substantial first-dose viral load reductions, cumulative anti-viral effect, is well tolerated in naive genotype HCV patients: a Phase 1 trial. J Hepatol. 2011;54(Supp 1):S478
- Jiang W, Zhu FG, Bhagat L, Yu D, Tang JX, Kandimalla ER, La Monica N, Agrawal S. A toll-like receptor 7, 8, and 9 antagonist inhibits Th1 and Th17 responses and inflammasome activation in a model of IL-23-induced psoriasis. J Investig Dermatol. 2013;133:1777–1784. doi: 10.1038/jid.2013.57. [DOI] [PubMed]
- El-Andaloussi S, Johansson HJ, Holm T, Langel U. A novel cell-penetrating peptide, M918, for efficient delivery of proteins and peptide nucleic acids. Mol Ther. 2007;15:1820–1826. doi: 10.1038/sj.mt.6300255. [DOI] [PubMed]
- Poeck H, Besch R, Hartmann G. 5′-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. Nat Med. 2008;14:1256–1263. doi: 10.1038/nm.1887. [DOI] [PubMed]
- Case CL. Regulating caspase-1 during infection: roles of NLRs, AIM2, and ASC. Yele J Biol Med. 2011;84:333–343. [PMC free article] [PubMed]
- Arnold AE, Malek-Adamian E, Le PU, Meng A, Martinez-Montero S, Petrecca K, Damha MJ, Sholchet MS. Antibody-antisense oligonucleotide conjugate downregulates a key gene in glioblastoma stem cells. Mol Ther Nucl Acids. 2018;11:518–527. doi: 10.1016/j.omtn.2018.04.004. [DOI] [PMC free article] [PubMed]
- Cuellar TL, Barnes D, Nelson C, Tanguay J, You S-F, Wen X, Scales SJ, Gesch J, Davis D, van Brabant SA, Leake D, et al. Systematic evaluation of antibody-mediated siRNA delivery using an industrial platform of THIOMAB-siRNA conjugates. Nucl Acids Res. 2015;43:1189–1203. doi: 10.1093/nar/gku1362. [DOI] [PMC free article] [PubMed]
- Langel U. Methods and protocols Methods in molecular biology. 2nd edn. Springer; New York, NY: 2015. Cell-penetrating peptides.
- Jearawiriyapaisarn N, Moulton HM, Buckley B, Roberts J, Sazani P, Fucharoen S, Iversen PL, Kole R. Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx mice. Mol Ther. 2008;16:1624–1629. doi: 10.1038/mt.2008.120. [DOI] [PMC free article] [PubMed]
- Passini MA, Hanson GJ. Exon skipping oligomer conjugates for muscular dystrophy. 2018
- Betts C, Saleh AF, Arzumanov AA, Hammond SM, Godfrey C, Coursindel T, Gait MJ, Wood MJA. A new generation of peptide-oligonucleotide conjugates with improved cardiac exon skipping activity for Duchenne muscular dystrophy treatment. Mol Ther Nucl Acids. 2012;1:e38 doi: 10.1038/mtna.2012.30. [DOI] [PMC free article] [PubMed]
- Klein AF, Varela M, Arandel L, Holland A, Naouar N, Arzumanov A, Seoane D, Revillod L, Bassez G, Ferry A, Jauvin D, et al. Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice. J Clin Investig. 2019;129:4739–4744. doi: 10.1172/JCI128205. [DOI] [PMC free article] [PubMed]
- Juliano RL. The delivery of therapeutic oligonucleotides. Nucl Acids Res. 2016;14:6518–6548. doi: 10.1093/nar/gkw236. [DOI] [PMC free article] [PubMed]
- Bacsa B, Horváti K, Bosze S, Andreae F, Kappe CO. Solid-phase synthesis of difficult peptide sequences at elevated temperatures: a critical comparison of microwave and conventional heating technologies. J Org Chem. 2008;73:7532–7542. doi: 10.1021/jo8013897. [DOI] [PubMed]
- Shubham S, Lin L-H, Udofot O, Krupse S, Giangrande PH. In: Advances in nucleic acid therapeutics. Agrawal S, Gait MJ, editors. Royal Society of Chemistry; London: 2019. Prostate-specific membrane antigen (PMSA) aptamers for prostate cancer imaging and therapy; pp. 339–366.
- Zon G. In: Advances in nucleic acids therapeutics. Agrawal S, Gait MJ, editors. Royal Society of Chemistry; London: 2019. Aptamers and clinical applications; pp. 367–399.
- Strenkowska M, Grzela R, Majewski M, Wnek K, Kowalski J, Lukaszewicz M, Zuberek J, Darzynkiewicz E, Kuhn AN, Sahin U, Jemielty J. Cap analogs modified with 1,2-dithiodiphosphate moiety protect mRNA from decapping and enhance its translational potential. Nucl Acids Res. 2016;44:9578–9590. doi: 10.1093/nar/gkw896. [DOI] [PMC free article] [PubMed]
- Andries O, McCafferty S, De Smedt SC, Weiss R, Sanders NN, Kitada T. N (1)-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J Control Release. 2015;217:337–344. doi: 10.1016/j.jconrel.2015.08.051. [DOI] [PubMed]
- Svitkin YV, Cheng YM, Chakraborty T, Presnyak V, John M, Sonenberg N. N1-methyl-pseudouridine in mRNA enhances translation through eIF2-α-dependent and independent mechanisms by increasing ribosome density. Nucl Acids Res. 2017;45:6023–6036. doi: 10.1093/nar/gkx135. [DOI] [PMC free article] [PubMed]
- Oberli MA, Rechmuth AM, Dorkin JR, Mitchell MJ, Fenton OS, Jaklenec A, Anderson DG, Langer R, Blankschtein D. Lipid nanoparticle assisted mRNA delivery for potent cancer immunotherapy. Nano Lett. 2017;17:1326–1335. doi: 10.1021/acs.nanolett.6b03329. [DOI] [PMC free article] [PubMed]
- Yin H, Song C-Q, Suresh S, Wu Q, Walsh S, Rhym LH, Mintzer E, Bolukbasi MF, Zhu LJ, Kauffman K, Mou H, et al. Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing. Nat Biotech. 2017;35:1179–1187. doi: 10.1038/nbt.4005. [DOI] [PMC free article] [PubMed]
- Hendel A, Bak RO, Clark JT, Kennedy AB, Ryan DE, Roy S, Steinfeld I, Lunstad BD, Kaiser RJ, Wilkens AB, Bacchette R, et al. Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells. Nat Biotech. 2015;33:985–989. doi: 10.1038/nbt.3290. [DOI] [PMC free article] [PubMed]
- Cromwell CR, Sung K, Park J, Krysler AR, Jovel J, Kim SK, Hubbard BP. Incorporation of bridged nucleic acids into CRISPR RNAs improves Cas9 endonuclease specificity. Nat Commun. 2018;9:1448. doi: 10.1038/s41467-018-03927-0. [DOI] [PMC free article] [PubMed]
- Geny S, Hosseini ES, Concordet J-P, Giovan-nangeli C. In: Advances in nucleic acid therapeutics. Agrawal S, Gait MJ, editors. Royal Society of Chemistry; London: 2019. CRISPR-based technologies for genome engineering: properties, current improvements and applications in medicine; pp. 400–433.
