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• W3207074037 endingPage "1292" @default.
• W3207074037 startingPage "1281" @default.
• W3207074037 abstract "Antisense oligonucleotides (ASOs) have emerged as a promising novel drug modality that aims to address unmet medical needs. A record of six ASO drugs have been approved since 2016, and more candidates are in clinical development. ASOs are the most advanced class within the RNA-based therapeutics field.This review highlights the two major backbones that are currently used to build the most advanced ASO platforms - the phosphorodiamidate morpholino oligomers (PMOs) and the phosphorothioates (PSs). The absorption, distribution, metabolism, and excretion (ADME) properties of the PMO and PS platforms are discussed in detail.Understanding the ADME properties of existing ASOs can foster further improvement of this cutting-edge therapy, thereby enabling researchers to safely develop ASO drugs and enhancing their ability to innovate.2'-MOE, 2'-O-methoxyethyl; 2'PS, 2 modified PS; ADME, absorption, distribution, metabolism, and excretion; ASO, antisense oligonucleotide; AUC, area under the curve; BNA, bridged nucleic acid; CPP, cell-penetrating peptide; CMV, cytomegalovirus; CNS, central nervous system; CYP, cytochrome P; DDI, drug-drug interaction; DMD, Duchenne muscular dystrophy; FDA, Food and Drug Administration; GalNAc3, triantennary N-acetyl galactosamine; IT, intrathecal; IV, intravenous; LNA, locked nucleic acid; mRNA, messenger RNA; NA, not applicable; PBPK, physiologically based pharmacokinetics; PD, pharmacodynamic; PK, pharmacokinetic; PMO, phosphorodiamidate morpholino oligomer; PMOplus, PMOs with positionally specific positive molecular charges; PPMO, peptide-conjugated PMO; PS, phosphorothioate; SC, subcutaneous; siRNA, small-interfering RNA; SMA, spinal muscular atrophy." @default.
• W3207074037 created "2021-10-25" @default.
• W3207074037 creator A5053949796 @default.
• W3207074037 creator A5076511944 @default.
• W3207074037 creator A5077041781 @default.
• W3207074037 date "2021-10-22" @default.
• W3207074037 modified "2023-10-06" @default.
• W3207074037 title "Antisense oligonucleotides: absorption, distribution, metabolism, and excretion" @default.
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• W3207074037 doi "https://doi.org/10.1080/17425255.2021.1992382" @default.
• W3207074037 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34643122" @default.
• W3207074037 hasPublicationYear "2021" @default.
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