ArticleCPT: pharmacometrics & systems pharmacology2025
Modeling and Simulation Identifies Endocytosis Uptake Rate and Fraction Unbound as Important Predictors of Oligonucleotide Pharmacokinetics.
Article in CPT: pharmacometrics & systems pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Engineering the Future of Precision Medicine: A Comprehensive Guide to RNA Therapeutics.Current issues in molecular biology · 2026Review
- Industry Practices in Oligonucleotide Tissue Biodistribution Assessment: An IQ consortium Cross-Industry Survey of Current Approaches and Emerging Trends.The AAPS journal · 2026Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic oligonucleotides (TOs) represent an emerging modality, which offers a promising alternative treatment option, particularly for intracellular targets. The two types of TOs, antisense oligonucleotides (ASO) and small interfering RNAs (siRNAs), distribute highly into tissues, especially into the liver and the kidneys. However, molecular processes at the cellular level such as the uptake into the cell, endosomal escape, binding to the target mRNA, and redistribution back to the systemic circulation are not well characterized because experimental data and assays are lacking. We developed a whole-body PBPK model for TOs and verified the predictive performance against clinically observed data for three ASOs and five siRNAs. The predicted concentration-time profiles were in accordance with the clinically observed data for all investigated TOs, and all pharmacokinetic parameters were predicted within twofold. Sensitivity analysis with the evaluated PBPK model revealed that the endocytosis uptake rate and the fraction unbound in plasma impact the peak concentration (C
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