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Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics

Author(s)
Kauffman, Kevin John; Xing, Yiping; Shaw, Taylor E.; Mir, Faryal; Dlott, Chloe C.; Langer, Robert S; Anderson, Daniel Griffith; Wang, Eric T; Dahlman, James E.; ... Show more Show less
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Abstract
Nucleic acid therapeutics are limited by inefficient delivery to target tissues and cells and by an incomplete understanding of how nanoparticle structure affects biodistribution to off-target organs. Although thousands of nanoparticle formulations have been designed to deliver nucleic acids, most nanoparticles have been tested in cell culture contexts that do not recapitulate systemic in vivo delivery. To increase the number of nanoparticles that could be tested in vivo, we developed a method to simultaneously measure the biodistribution of many chemically distinct nanoparticles. We formulated nanoparticles to carry specific nucleic acid barcodes, administered the pool of particles, and quantified particle biodistribution by deep sequencing the barcodes. This method distinguished previously characterized lung- and liver- targeting nanoparticles and accurately reported relative quantities of nucleic acid delivered to tissues. Barcode sequences did not affect delivery, and no evidence of particle mixing was observed for tested particles. By measuring the biodistribution of 30 nanoparticles to eight tissues simultaneously, we identified chemical properties promoting delivery to some tissues relative to others. Finally, particles that distributed to the liver also silenced gene expression in hepatocytes when formulated with siRNA. This system can facilitate discovery of nanoparticles targeting specific tissues and cells and accelerate the study of relationships between chemical structure and delivery in vivo
Date issued
2017-01
URI
http://hdl.handle.net/1721.1/113871
Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science; Koch Institute for Integrative Cancer Research at MIT
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Dahlman, James E., et al. “Barcoded Nanoparticles for High Throughput in Vivo Discovery of Targeted Therapeutics.” Proceedings of the National Academy of Sciences, vol. 114, no. 8, Feb. 2017, pp. 2060–65. © 2017 National Academy of Sciences
Version: Final published version
ISSN
0027-8424
1091-6490

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