ArticleBiophysical journal2005
Molecular and cellular barriers limiting the effectiveness of antisense oligonucleotides.
Article in Biophysical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 30 citations in OpenAlex.
- Chloroquine and cytosolic galectins affect endosomal escape of antisense oligonucleotides after Stabilin-mediated endocytosis.Molecular therapy. Nucleic acids · 2023Article
- Clinical Pharmacokinetics of Approved RNA Therapeutics.International journal of molecular sciences · 2023Review
- Endosomal Escape of Antisense Oligonucleotides Internalized by Stabilin Receptors Is Regulated by Rab5C and EEA1 During Endosomal Maturation.Nucleic acid therapeutics · 2018Article
- Enhancing the cytotoxicity of chemoradiation with radiation-guided delivery of anti-MGMT morpholino oligonucleotides in non-methylated solid tumors.Cancer gene therapy · 2017Article
- Rheological Properties of DNA Molecules in Solution: Molecular Weight and Entanglement Influences.Polymers · 2016Article
- A Kinetic Model Explains Why Shorter and Less Affine Enzyme-recruiting Oligonucleotides Can Be More Potent.Molecular therapy. Nucleic acids · 2014Article
- Prediction of antisense oligonucleotides using structural and thermodynamic motifs.Bioinformation · 2012Article
- Biomimetic high density lipoprotein nanoparticles for nucleic acid delivery.Nano letters · 2011Article
- Endocytosis and signalling: a meeting with mathematics.Molecular oncology · 2009Review
- Oligonucleotide loading determines cellular uptake of DNA-modified gold nanoparticles.Nano letters · 2007Article
- Interplay of polyethyleneimine molecular weight and oligonucleotide backbone chemistry in the dynamics of antisense activity.Nucleic acids research · 2007Article
- Poly(propylacrylic acid) enhances cationic lipid-mediated delivery of antisense oligonucleotides.Biomacromolecules · 2006Article
- Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging.Nucleic acids research · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Antisense oligonucleotides present a powerful means to inhibit expression of specific genes, but their effectiveness is limited by factors including cellular delivery, biochemical attack, and poor binding to target. We have developed a systems model of the processes required for an antisense oligonucleotide to enter, gain access to its target mRNA, and exert activity in a cell. The model accurately mimics observed trends in antisense effectiveness with the stability of the oligonucleotide backbone and with the affinity/kinetics of binding to the mRNA over the time course of inhibition. By varying the model parameters within the physically realizable range, we note that the major molecular and cellular barriers to antisense effectiveness are intracellular trafficking, oligonucleotide-mRNA binding rate, and nuclease degradation of oligonucleotides, with a weaker dependence on total cellular uptake than might be expected. Furthermore, the model may serve as a predictive tool to design and test strategies for the cellular use of antisense oligonucleotides. The use of integrated mathematical modeling can play a significant role in the development of antisense and related technologies.
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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.