ArticleMolecular therapy. Nucleic acids2019
Metabolite Profiling of the Antisense Oligonucleotide Eluforsen Using Liquid Chromatography-Mass Spectrometry.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 55 citations in OpenAlex.
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- Development of a Versatile High-through-put Oligonucleotide LC-MS Method to Accelerate Drug Discovery.AAPS PharmSciTech · 2024Article
- Current Status of Oligonucleotide-Based Protein Degraders.Pharmaceutics · 2023Review
- Bioanalysis of Oligonucleotide by LC-MS: Effects of Ion Pairing Regents and Recent Advances in Ion-Pairing-Free Analytical Strategies.International journal of molecular sciences · 2022Review
- Development of the Method for Nusinersen and Its Metabolites Identification in the Serum Samples of Children Treated with Spinraza for Spinal Muscular Atrophy.International journal of molecular sciences · 2022Article
- Oligonucleotides Isolation and Separation-A Review on Adsorbent Selection.International journal of molecular sciences · 2022Review
- Targeting fibrosis, mechanisms and cilinical trials.Signal transduction and targeted therapy · 2022Review
- Analysis of Oligonucleotide Biodistribution and Metabolization in Experimental Animals.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Instability Mechanism of Osimertinib in Plasma and a Solving Strategy in the Pharmacokinetics Study.Frontiers in pharmacology · 2022Article
- Destruction of DNA-Binding Proteins by Programmable Oligonucleotide PROTAC (O'PROTAC): Effective Targeting of LEF1 and ERG.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Safety Testing of an Antisense Oligonucleotide Intended for Pediatric Indications in the Juvenile Göttingen Minipig, including an Evaluation of the Ontogeny of Key Nucleases.Pharmaceutics · 2021Article
- Novel advances in biotransformation and bioactivation research - 2020 year in review.Drug metabolism reviews · 2021Article
- Pharmacokinetics and Proceedings in Clinical Application of Nucleic Acid Therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Studying in vitro metabolism of the first and second generation of antisense oligonucleotides with the use of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.Analytical and bioanalytical chemistry · 2020Article
- Review
- Introducing an In Vitro Liver Stability Assay Capable of Predicting the In Vivo Pharmacodynamic Efficacy of siRNAs for IVIVC.Molecular therapy. Nucleic acids · 2020Article
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- Combination Therapy Using Inhalable GapmeR and Recombinant ACE2 for COVID-19.Frontiers in molecular biosciences · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eluforsen (previously known as QR-010) is a 33-mer 2'-O-methyl modified phosphorothioate antisense oligonucleotide targeting the F508del mutation in the gene encoding CFTR protein of cystic fibrosis patients. In this study, eluforsen was incubated with endo- and exonucleases and mouse liver homogenates to elucidate its in vitro metabolism. Mice and monkeys were used to determine in vivo liver and lung metabolism of eluforsen following inhalation. We developed a liquid chromatography-mass spectrometry method for the identification and semi-quantitation of the metabolites of eluforsen and then applied the method for in vitro and in vivo metabolism studies. Solid-phase extraction was used following proteinase K digestion for sample preparation. Chain-shortened metabolites of eluforsen by 3' exonuclease were observed in mouse liver in an in vitro incubation system and by either 3' exonuclease or 5' exonuclease in liver and lung samples from an in vivo mouse and monkey study. This study provides approaches for further metabolite characterization of 2'-ribose-modified phosphorothioate oligonucleotides in in vitro and in vivo studies to support the development of oligonucleotide therapeutics.
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