ArticleBiophysical journal2007
Understanding intracellular transport processes pertinent to synthetic gene delivery via stochastic simulations and sensitivity analyses.
Article in Biophysical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed.
- Anticodon-edited transfer RNAs (ACE-tRNAs) encoded as therapeutic nonviral minimal DNA vectors.Nucleic acids research · 2026Article
- Model-Informed Drug Development Applications and Opportunities in mRNA-LNP Therapeutics.Clinical pharmacology and therapeutics · 2025Review
- Anticodon Edited Transfer RNAs (ACE-tRNAs) Encoded as Therapeutic Nonviral Minimal DNA Vectors.bioRxiv : the preprint server for biology · 2025Article
- Trafficking in cancer: from gene deregulation to altered organelles and emerging biophysical properties.Frontiers in cell and developmental biology · 2024Review
- Delivery of drugs, proteins, and nucleic acids using inorganic nanoparticles.Advanced drug delivery reviews · 2020Review
- Kinome-level screening identifies inhibition of polo-like kinase-1 (PLK1) as a target for enhancing non-viral transgene expression.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Non-viral vectors for gene-based therapy.Nature reviews. Genetics · 2014Review
- Article
- Intracellular delivery and trafficking dynamics of a lymphoma-targeting antibody-polymer conjugate.Molecular pharmaceutics · 2012Article
- Subcellular trafficking and transfection efficacy of polyethylenimine-polyethylene glycol polyplex nanoparticles with a ligand to melanocortin receptor-1.Journal of controlled release : official journal of the Controlled Release Society · 2012Article
- Nucleic acid delivery: the missing pieces of the puzzle?Accounts of chemical research · 2012Review
- Non-Markovian polymer reaction kinetics.Nature chemistry · 2012Article
- Real-time gene delivery vector tracking in the endo-lysosomal pathway of live cells.Microscopy research and technique · 2012Article
- Understanding nonviral nucleic acid delivery with quantum dot-FRET nanosensors.Nanomedicine (London, England) · 2012Review
- Modeling the step of endosomal escape during cell infection by a nonenveloped virus.Biophysical journal · 2012Article
- Gene therapy from the perspective of systems biology.Current opinion in molecular therapeutics · 2010Review
- Balancing protection and release of DNA: tools to address a bottleneck of non-viral gene delivery.Journal of the Royal Society, Interface · 2010Review
- Gene therapy progress and prospects: synthetic polymer-based systems.Gene therapy · 2008Review
- Network analysis of endogenous gene expression profiles after polyethyleneimine-mediated DNA delivery.The journal of gene medicineArticle
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A major challenge in synthetic gene delivery is to quantitatively predict the optimal design of polymer-based gene carriers (polyplexes). Here, we report a consistent, integrated, and fundamentally grounded computational methodology to address this challenge. This is achieved by accurately representing the spatio-temporal dynamics of intracellular structures and by describing the interactions between gene carriers and cellular components at a discrete, nanoscale level. This enables the applications of systems tools such as optimization and sensitivity analysis to search for the best combination of systems parameters. We validate the approach using DNA delivery by polyethylenimine as an example. We show that the cell topology (e.g., size, circularity, and dimensionality) strongly influences the spatiotemporal distribution of gene carriers, and consequently, their optimal intracellular pathways. The model shows that there exists an upper limit on polyplexes' intracellular delivery efficiency due to their inability to protect DNA until nuclear entry. The model predicts that even for optimally designed polyethylenimine vectors, only approximately 1% of total DNA is delivered to the nucleus. Based on comparison with gene delivery by viruses, the model suggests possible strategies to significantly improve transfection efficiencies of synthetic gene vectors.
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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.