Open AccessQuinine copolymer reporters promote efficient intracellular DNA delivery and illuminate a protein-induced unpackaging mechanism
Author(s) -
Craig Van Bruggen,
David Punihaole,
Allison R. Keith,
Andrew J. Schmitz,
Jakub Tolar,
Renee R. Frontiera,
Theresa M. Reineke
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2016860117
Subject(s) - nucleic acid , quinine , gene delivery , dna , polymer , intracellular , nanotechnology , chemistry , biophysics , microbiology and biotechnology , genetic enhancement , biochemistry , gene , biology , materials science , organic chemistry , malaria , immunology
Significance 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 polymers unpackage their cargo. We developed a quinine-containing polymer that shows exceptional gene delivery activity. A key aspect of this platform is that the quinine serves as a reporter for DNA binding using Raman spectroscopy. This allows us to track cargo release inside the cell using Raman 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 nucleic acid delivery mechanisms and to be used for clinical therapy applications.