| Intracellular Transport of Synthetic Gene Vectors (Computational) Nishit Doshi Gene therapy is rapidly evolving as a therapeutic strategy to treat inherited and acquired diseases. The principal of gene therapy is simple, that is, putting corrective genetic material into cells to alleviate the symptoms of the disease. In practice, delivery of a gene to the nucleus of the targeted cells is a challenging task due to a variety of barriers that a gene delivery vehicle (vector) has to overcome in order to breach into the nucleus. To successfully deliver DNA into the nucleus, gene vectors, viral or synthetic, 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 transport processes, especially in an integrated mode, is still lacking. The objective of the proposed study is to develop an integrated and comprehensive computational framework, SimCell (Simulation of Discrete Nanoscale Transports in Cell), and to describe, analyze and predict the physical processes associated with gene delivery at the local, cellular and sub- cellular level. These in silico experiments can be integrated into the experimental cycle to guide the wet-lab process, facilitate experimental research, and reduce experimental costs. Development of SimCell is based on the following modeling objectives:
|