The importance of physical structure of cationic peptides on siRNA and DNA packaging and delivery

What is it about?

Gene and siRNA therapy technologies provides the ideal platform for precision medicine, however, delivering the nucleic acids into specific cells and tissues remains challenging. Despite the fact that there has been a wealth of systems developed for nucleic acid delivery in the last 20 years, success in clinics is limited. Peptide based nucleic acid delivery systems are one of the most widely used vectors, but rationales or rules to improve nucleic acid packaging and delivery has only started to emerge. To gain insights on the structure-activity relationship for better designing a peptide-based nucleic acid system, this study investigates the relationship of the physical structures of the widely used polylysines on plasmid DNA and siRNA packaging and delivery. Our study suggests that small and linear cationic peptides are effective for plasmid DNA but not siRNA delivery. siRNA has a more rigid physical structure than plasmid DNA, and therefore siRNA requires a more flexible structure, such as branched peptides and/or peptide dendrimers, for packaging and delivery.

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