CATIONIC LIPID PHASE BEHAVIOR AND ITS IMPORTANCE TO TRANSFECTION

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Positively charged lipids can be used to deliver DNA to cells, and are considered the most promising non-viral gene carriers. They form complexes (lipoplexes) with the polyanionic DNA. The mechanism of lipofection is still largely unknown and the long-term objective of the project is to shed light on the lipofection mechanisms so that lipoplexes can be formulated with optimum efficiency for gene therapy. Although lamellar phases are most familiar due to their relationship to biological membranes, lipids form variety of nonlamellar phases as well. Phase state affects virtually all properties of lipid dispersions, and has been found to influence lipofection efficiency. This project is focused on the relationship between lipid phase behavior and transfection, in particular on understanding how DNA is discharged from lipoplexes, and how that process relates to the phase behavior of carrier lipid/cellular lipid arrays. The project is predicated on the hypothesis that a key factor for DNA release in transfection is the structural evolution of the lipoplexes upon interaction with cellular lipids, and that the initial lipoplex structure is mainly important for the successful import of DNA to cells. Preliminary results revealed correlation between DNA release and phases formed in mixtures of cellular and cationic lipids. The specific aims include understanding the mechanism of DNA release from lipoplexes induced by cellular lipid mixtures, and looking for correlation of the cationic lipids chemical structure, their phase organization, and the efficiency of DNA release by cellular lipids, so that lipoplexes of predicted superior transfection efficacy can be formulated.