Synthesis of Chrysin Based Cationic Lipids: Plasmid Delivery and Transgene Expression

Abstract

Cationic lipids are attractive candidates for transgene delivery and expression and are safer alternatives to viral delivery vehicles. Here, we report the design, synthesis, characterization and transgene expression efficacies of a series of chrysin derived cationic lipids. A series of ten lipids of chrysin was synthesized by treating the 7-hydroxy group with dibromoalkane and further substitution of the bromo derivative with alkyl amines. The synthesized lipids were characterized spectroscopically. Parallel screening of the synthesized lipids for in vitro plasmid delivery expressing luciferase led to identification of several leads that demonstrated higher transgene expression when compared to the standard. Transgene expression efficacy was dependent on the chain length of the lipid. The influence of the various physicochemical properties on transgene expression efficacies was investigated. This study indicates that lipids derived from chrysin results in high levels of transgene expression and may be attractive for gene therapy applications.