Intracellular Trafficking of Polyamidoamine–Poly(ethylene glycol) Block Copolymers in DNA Delivery
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Langer_Intracellular trafficking.pdf
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Author(s)
Bonner, Daniel K.
Leung, Cheuk
Chen-Liang, Jane
Chingozha, Loice
Langer, Robert
Hammond, Paula T.
Date Issued
August 2011
Journal
Bioconjugate Chemistry
Publisher
American Chemical Society
Citation
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. .
Version
Author's final manuscript
Abstract
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.
Description
available in PMC 2012 August 17
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/bc200059v
