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Intern: Xuan An Truong, Contra Costa College Mentor: Tuan Dinh Faculty Supervisor: Samir Mitragotri Department: Chemical Engineering

INTRACELLULAR TRANSPORT PROCESSES

Viruses have been used as gene delivery vehicles in a number of gene therapy applications. To successfully deliver DNA into the nucleus, virus must facilitate cell-specific binding, internalization by endocytosis, escape from endocytic vesicles into the cytosol, cytoplasmic transport, translocation across the nuclear envelop, release/dissociation of gene in a form suitable for transcription, and finally expression of the delivered gene. A quantitative understanding of these physical processes, especially in an integrated mode, is still lacking. In the present study, we develop an integrative computational framework to describe physical processes involved in viral gene delivery. The framework relates biological functions of endocytic vesicles and molecular-level binding and trafficking events on microtubules to whole-cell distribution of viruses. We employ the model to study how motor-assisted transport influences accumulation of adenoviruses in the nuclear region and expression of viral genome. We also investigate the effects of nocodazole, a microtubule-depolymerizing drug on the overall transport efficiency. Model predictions are compared to experimental data available in literature.

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