Polymer-based vehicles that controllably deliver therapeutic nucleic acids to cells show great potential to develop safe and effective gene therapies. Realizing this potential, however, is limited by the lack of understanding of how polymeric vehicles unpackage and release their cargo in the cell. We address this problem by utilizing a novel quinine-containing polymeric vehicle that shows exceptional gene delivery activity. A key aspect of this platform is that the quinine serves as a reporter for DNA binding, which allows us to track cargo release inside the cell using chemical imaging. We find that proteins dominate the unpackaging of DNA encapsulated by these quinine polymers inside cells. This trackable delivery system should be broadly applicable to study gene delivery mechanisms, as well as be used for clinical therapy applications.
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