Intracellular Trafficking of Polyamidoamine–Poly(ethylene glycol) Block Copolymers in DNA Delivery
Author(s)Bonner, Daniel K.; Leung, Cheuk; Chen-Liang, Jane; Chingozha, Loice; Langer, Robert; Hammond, Paula T.; ... Show more Show less
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The delivery of nucleic acids has the potential to revolutionize medicine by allowing previously untreatable diseases to be clinically addressed. Viral delivery systems have shown immunogenicity and toxicity dangers, but synthetic vectors have lagged in transfection efficiency. Previously, we developed a modular, linear–dendritic block copolymer architecture with high gene transfection efficiency compared to commercial standards. This rationally designed system makes use of a cationic dendritic block to condense the anionic DNA and forms complexes with favorable endosomal escape properties. The linear block provides biocompatibility and protection from serum proteins, and can be functionalized with a targeting ligand. In this work, we quantitate performance of this system with respect to intracellular barriers to gene delivery using both high-throughput and traditional approaches. An image-based, high-throughput assay for endosomal escape is described and applied to the block copolymer system. Nuclear entry is demonstrated to be the most significant barrier to more efficient delivery and will be addressed in future versions of the system.
available in PMC 2012 August 17
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Chemical Engineering
American Chemical Society
Bonner, Daniel K., Cheuk Leung, Jane Chen-Liang, Loice Chingozha, Robert Langer, and Paula T. Hammond. Intracellular Trafficking of Polyamidoamine–Poly(ethylene Glycol) Block Copolymers in DNA Delivery. Bioconjugate Chemistry 22, no. 8 (August 17, 2011): 1519-1525. .
Author's final manuscript