BME MS Defense: Benjamin Danziger

Finite Element Modeling of Electroporation in the Pig Lung: Studies in Gene Transfer and Safety

The use of plasmid DNA (pDNA) for gene therapy in the lungs of mammals is quickly becoming a reality. The Dean Lab has developed an electroporation-based method for delivering pDNA to the lungs of living pigs. Before this method can be used in the clinical setting, it is necessary to demonstrate efficacy, both in terms of degree and distribution of gene expression, and the safety of the delivery mechanism.

By use of computer modeling with finite-element time-domain (FETD) methods, simulation of resultant electric fields were analyzed, giving both distribution and safety predictions of gene delivery. Upon reaching certain field strength requirements, it is believed that electroporation will occur, allowing uptake of pDNA into cells of the surrounding lung tissue. By analyzing the resulting current density, certain conclusions were made concerning distribution of gene expression and cardiac safety with transthoracic, pulmonary electroporation. All simulations were validated by physical experimentation. The final models created faithfully predict the qualitative distribution of gene delivery and expression in the right lower lobe of the pig lung following expression (greater than 80% concurrence between computational and experimental results) and confirm that pulmonary electroporation is safe in terms of cardiac injury.