Non-Viral Gene Transfection with Ultrasound: Is 100% Transfection Possible?

Abstract

Ultrasound has been used as a modality to enhance the transfection of cells, purportedly via entry of genetic material through defects in the cell membrane produced by bubble cavitation events. A mathematical model was created to simulate the cellular accumulation of damaging membrane insults due to stresses from shock waves produced by bubble collapse cavitation events. The simulation consists of randomly located cells subjected to shock waves from randomly distributed (in space and energy) collapse cavitations. The shock wave energy that is accumulated during more than 20,000 simulated events is compared to the threshold levels for killing and transfection, at which time the cell is assigned to be dead, transfected, or neither. The model results were compared to published experimental results, and the threshold levels were adjusted to match the model with the experiment. The results indicate that a population of cells has a distribution of killing thresholds. A lognormal distribution fits the experimental viability data adequately. Applying a similar distribution to the transfection threshold indicates that the transfection threshold has a higher value than the killing threshold. This model is based on the assumption that cell damage is cumulative; this and other assumptions are discussed. This model is also compared to the “blast radius” model published by others. The model indicates that cell fragility limits transfection of all cells.