Simulation of Viral Gene Delivery

摘要

Here we develop an integrative computational framework to model biophysical processes involved in viral gene delivery. The model uses reaction-diffusion-advection equations that describe intracellular trafficking in combination with kinetic equations that describe transcription and translation of the exogenous DNA. It relates molecular-level microtubular binding and trafficking events to whole-cell distribution of viruses. The approach makes use of current understanding of cellular processes and data from single-particle single-cell imaging experiments. We employ the model to study the influence of microtubule-mediated movements on nuclear targeting and gene expression of adenoviruses in HeLa and A549 cells. Effects of microtubule organization and dynamics and the presence of microtubule-destabilizing drug were analyzed and quantified. Model predictions agree well with experimental data available in literature. The paper serves as a guide for future theoretical and experimental efforts to understand viral gene delivery.