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Simulation of Viral Gene Delivery

A.T. Dinh, S. Mitragotri and T. Theofanous
University of California, Santa Barbara, US

Keywords:
adenovirus, viral gene delivery, intracellular transport, microtubule, motor-assisted transport, simulation, diffusion-advection-reaction equations

Abstract:
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. The model reveals two important parameters that characterize viral transport at the population level, namely, the effective velocity, Veff and the effective diffusion coefficient Deff. Veff measures virus’s net movement rate and Deff represents total dispersion rate. 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. 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.

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