Prediction and optimization of gene transfection and drug delivery by electroporation

Although electroporation is widely used for laboratory gene transfection and gaining increased importance for nonviral gene therapy, it is generally employed using trial-and-error optimization schemes for lack of methods to predict electroporation's effects on cells. Therefore, we used a statistical approach to quantitatively predict molecular uptake and cell viability following electroporation and show that it predicts both in vitro and in vivo results for a wide range of molecules, including DNA, in 60 different cell types. Mechanistically, this broad predictive ability suggests that electroporation is mediated primarily by lipid bilayer structure and only secondarily by cell-specific characteristics. For gene therapy applications, this approach should facilitate rational design of electroporation protocols.