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Significance Splice-switching antisense oligonucleotides (ASOs) represent a unique class of drug molecules with the US Food and Drug Administration approval of Exondys 51, Vyondys 53, Amondys 45, and Viltepso for… Click to show full abstract
Significance Splice-switching antisense oligonucleotides (ASOs) represent a unique class of drug molecules with the US Food and Drug Administration approval of Exondys 51, Vyondys 53, Amondys 45, and Viltepso for the treatment of Duchenne muscular dystrophy (DMD). Phosphorodiamidate morpholino oligomer (PMO) chemistry currently utilized for these drugs has significant limitations. PMOs show rapid kidney clearance and poor cellular uptake that leads to high and costly dosages. Therefore, it is crucial to develop next-generation splice-switching oligonucleotide chemistries with improved efficacy, safety, and biodistribution. The research outlined in this manuscript is highly significant as it demonstrates the impact of “Thiomorpholinos” as a robust and cost-effective splice-switching ASO platform that can be tested for enhanced biological activity and reduced toxicity relative to other chemistries.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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