ArticleMolecular therapy. Nucleic acids2020
Introducing an In Vitro Liver Stability Assay Capable of Predicting the In Vivo Pharmacodynamic Efficacy of siRNAs for IVIVC.
Article in Molecular therapy. Nucleic acids, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Considerations and recommendations for assessment of plasma protein binding and drug-drug interactions for siRNA therapeutics.Nucleic acids research · 2022Pooled it
- Pharmacokinetic/Pharmacodynamic Translation and Model-Informed Drug Development for Oligonucleotide Therapeutics.Journal of clinical pharmacology · 2026Review
- 2'-Ribose-modified nucleotides: A strategy for reducing off-target effects of oligonucleotide drugs.Molecular therapy. Nucleic acids · 2026Article
- Chemical control of 2'-hydroxyl-dependent Cas9 target engagement enables CRISPR RNA ribose replacement.bioRxiv : the preprint server for biology · 2026Article
- Modeling and Simulation Identifies Endocytosis Uptake Rate and Fraction Unbound as Important Predictors of Oligonucleotide Pharmacokinetics.CPT: pharmacometrics & systems pharmacology · 2025Article
- Translational and clinical development of therapeutic siRNA and ASOs: current industry practices, perspectives, and recommendations.Nucleic acids research · 2025Article
- Article
- Tissue pharmacokinetics of antisense oligonucleotides.Molecular therapy. Nucleic acids · 2024Article
- Self-delivering, chemically modified CRISPR RNAs for AAV co-delivery and genome editing in vivo.Nucleic acids research · 2024Article
- Pharmacokinetic and Pharmacodynamic Modeling of siRNA Therapeutics - a Minireview.Pharmaceutical research · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There has been a renewed interest in therapeutic small interfering RNAs (siRNAs) over the past few years. This is particularly the result of successful and efficient delivery of N-acetylgalactosamine (GalNAc)-conjugated siRNAs to the liver. In general, the lead selection process for siRNA drugs is faster and more straightforward than traditional small molecules. Nevertheless, many siRNAs of different sequences and chemical modification patterns must still be evaluated before arriving at a final candidate. One of the major difficulties in streamlining this workflow is the well-known phenomenon that the in vitro data obtained from oligonucleotides transfected into cells are not directly predictive of their in vivo activity. Consequently, all oligonucleotides with some degree of in vitro activity are typically screened in vivo before final lead selection. Here, we demonstrate that the stability of liver-targeting GalNAc-conjugated siRNAs in a mouse liver homogenate shows an acceptable correlation to their in vivo target knockdown efficacy. Therefore, we suggest the incorporation of an in vitro liver homogenate stability assay during the lead optimization process for siRNAs. The addition of this assay to a flow scheme may decrease the need for animal studies, and it could bring cost savings and increase efficiency in siRNA drug development.
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