Study on the role of polyethylenimine as gene delivery carrier using molecular dynamics simulations

Polyethylenimine (PEI) is known to be one of the most promising polymers to serve as a delivery carrier in gene therapy. Complexation between PEI molecules and nucleic acids results in nanoparticles that can subsequently enter cells for therapeutic treatment. Design of the carrier molecules for stabler complexation, better cell uptake, and lower cytotoxicity remains to be a challenge. Molecular dynamics (MD) simulations allow atomistic level examination of the complexation between PEI and nucleic acids, as well as the interaction of the complexes formed with other entities in the delivery path. It is a powerful tool in revealing the role of carrier molecules and guiding the design of more effective delivery systems. In this work, we first review the current status in studying complexation of PEI with nucleic acids and interaction between the complex formed and cell membrane. We have conducted preliminary MD simulations on several aspects of complexation between PEI and DNA. These results are presented to demonstrate how MD simulations can help understand the role of PEI in serving as a gene delivery carrier.