Biological membranes pose notorious barriers against the delivery of nucleic acids. By mimicking the naturally occurring cell penetrating peptides (CPPs), we recently developed guanidine-rich, cationic polypeptides with stable helical structure to mediate highly efficient trans-membrane gene delivery. The helical polypeptides imparted strong and helicity-dependent membrane activities, and thus displayed potent gene delivery efficiencies that outperformed commercial reagents by 1-2 orders of magnitude. Upon structural optimization including aromatic modification, topological manipulation (star, dendritic, or brush), and photochemical activation, these helical polypeptides were endowed with further enhanced membrane activities and gene delivery capabilities, which demonstrated potent capabilities for siRNA delivery to treat cancer or inflammatory diseases such as acute lung injury or myocardial ischemia reperfusion injury. To enable selective membrane activities, conformation transitionable polypeptides were developed, which could undergo helix-to-coil or coil-to-helix transition upon internal stimuli, thus realizing turn-on/off of the membrane penetrating properties.

Anti-cancer/anti-inflammation gene delivery via membrane-penetrating cationic helical polypeptides

2019 Fall National Meeting

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