Multi-level kinetic model of mRNA delivery via transfection of lipoplexes

PLoS One. 2014 Sep 19;9(9):e107148. doi: 10.1371/journal.pone.0107148. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation*
  • Endosomes / metabolism
  • Gene Transfer Techniques*
  • Kinetics
  • Models, Genetic*
  • RNA, Messenger / metabolism
  • Transfection / methods*

Substances

  • RNA, Messenger

Grant support

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) via project B1 within the SFB 1032, the Excellence Cluster ‘Nanosystems Initiative Munich (NIM)’, and FP7 EU grants NanoTransKinetics and Nano-MILE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.