(663a) Molecular Simulation Studies Relating Thermodynamics of Polycation-DNA Binding to Non-Viral DNA Delivery
In this talk I will present our recent work involving computational design of polymers as carriers for gene delivery. Viruses are extremely effective as gene delivery vectors but elicit dangerous immunogenic responses. Non-viral gene delivery agents, like polycations, while not as effective as viral vectors have a significant advantage of being non-immunogenic. Polycations have emerged as promising non-viral delivery agents due to their propensity to bind the polyanionic DNA backbone, neutralizing the negative charge of DNA backbone, and facilitating gene delivery. Recent experiments by our collaborators T. Emrick and coworkers  has shown that the architecture of poly-lysine affects, in a non-trivial manner , the efficiency of these polycations as transfection agents. Our work using molecular simulations, with both atomistic  and coarse-grained models, connects poly-L-lysine architecture to DNA binding thermodynamics, and explains the molecular reasons behind the experimentally observed trends in DNA delivery.
1. S.S. Parelkar, D. Chan-Seng, T. Emrick Reconfiguring polylysine architectures for controlling polyplex binding and non-viral transfection Biomaterials 32 (9) pp 2432-2444 (2011)
2. R. Elder, T. Emrick, and A. Jayaraman,'Understanding the effect of polylysine architecture on DNA binding using molecular dynamics simulations' Biomacromolecules 12 (11), pp 3870-3879 (2011)