ArticleMolecular therapy. Nucleic acids2019
Modeling the Kinetics of Lipid-Nanoparticle- Mediated Delivery of Multiple siRNAs to Evaluate the Effect on Competition for Ago2.
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 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.
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Who cites it
4 citing papers in PubMed, 14 citations in OpenAlex.
- Multiscale modeling guided potency assessment of mRNA-lipid nanoparticles.Molecular therapy. Nucleic acids · 2026Article
- Mechanistic intracellular PK/PD modeling to inform development strategies for small interfering RNA therapeutics.Molecular therapy. Nucleic acids · 2025Article
- Pharmacokinetic and Pharmacodynamic Modeling of siRNA Therapeutics - a Minireview.Pharmaceutical research · 2022Review
- Therapeutic siRNA: state of the art.Signal transduction and targeted therapy · 2020Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug combinations can improve the control of diseases involving redundant and highly regulated pathways. Validating a multi-target therapy early in drug development remains difficult. Small interfering RNAs (siRNAs) are routinely used to selectively silence a target of interest. Owing to the ease of design and synthesis, siRNAs hold promise for combination therapies. Combining siRNAs against multiple targets remains an attractive approach to interrogating highly regulated pathways. Currently, questions remain regarding how broadly such an approach can be applied, since siRNAs have been shown to compete with one another for binding to Argonaute2 (Ago2), the protein responsible for initiating siRNA-mediated mRNA degradation. Mathematical modeling, coupled with in vitro and in vivo experiments, led us to conclude that endosomal escape kinetics had the highest impact on Ago2 depletion by competing lipid-nanoparticle (LNP)-formulated siRNAs. This, in turn, affected the level of competition observed between them. A future application of this model would be to optimize delivery of desired siRNA combinations in vitro to attenuate competition and maximize the combined therapeutic effect.
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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 OpenQuestion graph.