The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides
Abstract
:1. Introduction
2. The Use of Oligonucleotides in Therapy and Diagnostics and the Mechanisms behind Them
3. Artificial Nucleic Acids
3.1. Base Modified Nucleic Acids
3.2. Sugar-Modified Nucleic Acids
3.3. Nucleotides with Modified Backbones
4. Oligonucleotide Drugs
4.1. Fomivirsen
4.2. Pegaptanib
4.3. Mipomersen
4.4. Eteplirsen
4.5. Defibrotide
4.6. Nusinersen
4.7. Patisiran
4.8. Inotersen
4.9. Milasen
4.10. Volanesorsen
4.11. Givosiran
4.12. Golodirsen
4.13. Viltolarsen
4.14. Inclisiran
4.15. Lumasiran
4.16. Casimersen
4.17. Tozinameran
4.18. Elasomeran
5. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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INN Name | Approval | Chemical Structure | Mechanism of Action | Disease |
---|---|---|---|---|
Fomivirsen (Vitravene) | FDA 1998 EMA 1999 | PS | antisense | cytomegalovirus retinitis |
Pegaptanib (Macugen) | FDA 2004 | 2′-O-Me, 2′-F, PEG-conjugate, 3′-inverted nucleotide | aptamer | age related macula degeneration |
Mipomersen (Kynamro) | FDA 2013 | PS, 2′-O-MOE gapmer, 5-Me-C | antisense | familial hypercholesterolaemia |
Eteplirsen (Exondys 51) | FDA 2016 | PMO | antisense, splicing modulation | Duchenne muscular dystrophy |
Defibrotide (Defitelio) | FDA 2016 | mixture of ds and ss ODNs with 50 bp average length | aptamer, complex | Sinusoidal obstruction syndrome |
Nusinersen (Spinraza) | FDA 2016 EMA 2017 | 2′-O-MOE, PS, 5-Me-C | antisense, splicing modulation | Spinal muscular atrophy |
Patisiran (Onpattro) | FDA 2018 EMA 2018 | 2′-OMe | RNA interference | Hereditary transthyretin mediated amyloidosis |
Inotersen (Tegsedi) | FDA 2018 EMA 2018 | PS, 2′-O-MOE, 5-Me-C | antisense | Hereditary transthyretin mediated amyloidosis |
Milasen | FDA 2017 | 2′-O-MOE | antisense, splicing modulation | Batten’s disease (patient-costumized) |
Volanesorsen (Waylivra) | EMA 2019 | PS, 2′-O-MOE, 5-Me-C | antisense | Familial chylomicronemia |
Givosiran (Givlaari) | FDA 2019 EMA 2020 | PS, 2′-F, 2′-OMe, GalNAc-conjugate | RNA interference | Acute hepatic porphyria |
Golodirsen (Vyondys 53) | FDA 2019 | PMO | antisense, splicing modulation | Duchenne muscular dystrophy |
Viltolarsen (Viltepso) | FDA 2020 | PMO | antisense, splicing modulation | Duchenne muscular dystrophy |
Casimersen (Amondys 45) | FDA 2021 | PMO | antisense, splicing modulation | Duchenne muscular dystrophy |
Inclisiran (Leqvio) | EMA 2020 | PS, 2′-F, 2′-OMe, GalNAc-conjugate | RNA interference | primary hypercholesterolaemia |
Lumasiran (Oxlumo) | FDA 2020 EMA 2020 | PS, 2′-F, 2′-OMe, GalNAc-conjugate | RNA interference | primary hyperoxaluria |
Tozinameran (Comirnaty) | FDA 2020 EMA 2020 | m1ψ, 2′-OMe, 5′-cap | mRNA vaccine | COVID-19 |
Elasomeran (Soikevax) | FDA 2020 EMA 2020 | m1ψ, 5′-cap | mRNA vaccine | COVID-19 |
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Bege, M.; Borbás, A. The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides. Pharmaceuticals 2022, 15, 909. https://doi.org/10.3390/ph15080909
Bege M, Borbás A. The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides. Pharmaceuticals. 2022; 15(8):909. https://doi.org/10.3390/ph15080909
Chicago/Turabian StyleBege, Miklós, and Anikó Borbás. 2022. "The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides" Pharmaceuticals 15, no. 8: 909. https://doi.org/10.3390/ph15080909
APA StyleBege, M., & Borbás, A. (2022). The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides. Pharmaceuticals, 15(8), 909. https://doi.org/10.3390/ph15080909