Multi-Level Kinetic Model of mRNA Delivery via Transfection of Lipoplexes
| Autor: | Carolin Leonhardt, Joachim O. Rädler, Thomas Ligon |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Biophysical Simulations
Work (thermodynamics) Stochastic modelling Biophysics lcsh:Medicine Condensed Matter Endosomes Gene delivery Biology Transfection Biochemistry Biochemical Simulations Medicine and Health Sciences Pharmacokinetics Computer Simulation RNA Messenger lcsh:Science Molecular Biology Techniques Molecular Biology Pharmacology Messenger RNA Multidisciplinary Models Genetic Systems Biology Physics lcsh:R Gene Transfer Techniques Biology and Life Sciences Computational Biology Gene Therapy Condensed Matter Physics Molecular biology Expression (mathematics) Kinetics Bionanotechnology Physical Sciences Simulated annealing lcsh:Q Biological system Research Article Biotechnology Free parameter |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 9, p e107148 (2014) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0107148 |
| Popis: | Recent work on the use of mRNA lipoplexes for gene delivery demonstrates the need for a mathematical model that simulates and predicts kinetics and transfection efficiency. The small copy numbers involved make it necessary to use stochastic models and include statistical analysis of the variation observed in the experimental data. The modeling requirements are further complicated by the multi-level nature of the problem, where mRNA molecules are contained in lipoplexes, which are in turn contained in endosomes, where each of these entities displays a behavior of its own. We have created a mathematical model that reproduces both the time courses and the statistical variance observed in recent experiments using single-cell tracking of GFP expression after transfection. By applying a few key simplifications and assumptions, we have limited the number of free parameters to five, which we optimize to match five experimental determinants by means of a simulated annealing algorithm. The models demonstrate the need for modeling of nested species in order to reproduce the shape of the dose-response and expression-level curves. |
| Databáze: | OpenAIRE |
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