ArticlePharmacology research & perspectives2025
In Vitro Structure-Activity Relationship Stability Study of Antisense Oligonucleotide Therapeutics Using Biological Matrices and Nucleases.
Article in Pharmacology research & perspectives, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed.
- Targeting ARF6-SUCNR1 Axis: Antisense Oligonucleotide Adjuvants for Neutrophil Immunometabolism.International journal of molecular sciences · 2026Review
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- Organyl 5'-Phosphates in siRNA Guide Strands: Structure-Function Relationships Governing Anchoring in Argonaute 2 and Metabolic Stability.bioRxiv : the preprint server for biology · 2026Article
- Clickable RNA via 4'-Bioconjugate chemistry · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The primary degradation pathway for antisense oligonucleotides (ASOs) involves endonuclease and exonuclease-mediated breakdown. The effect of various chemical modifications on the stability of oligonucleotides has not been systematically investigated. The aim of this study was to develop in vitro assays to predict in vivo metabolism of ASOs. Stability studies of ASOs with varying phosphorothioate/phosphodiester (PS/PO) content were conducted using nucleolytic matrices (snake venom 3'-exonuclease phosphodiesterase I [PDEI], mouse serum, and mouse liver homogenate) and analyzed by gel electrophoresis and liquid chromatography with ultraviolet and mass spectrometry detection (LC-UV/MS). Both sequence composition and backbone chemistry play important roles in influencing the stability of ASOs. Nucleolytic sensitivity observed with PDEI and mouse serum shows that ASOs with one PO modification in the backbone have higher stability than ASOs having two or three PO links, and with a lower PO content, the sequence has a larger influence on stability. Furthermore, the impact of a 5-methylcytidine nucleoside (
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.