Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles
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nihms598014.pdf
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Author(s)
Chen, Delai
Veiseh, Omid
Pelet, Jeisa
Yin, Hao
Dong, Yizhou
Anderson, Daniel Griffith
Eltoukhy, Ahmed A.
Date Issued
May 2014
Journal
Biomaterials
Publisher
Elsevier
Citation
Eltoukhy, Ahmed A. et al. “Nucleic Acid-Mediated Intracellular Protein Delivery by Lipid-like Nanoparticles.” Biomaterials 35.24 (2014): 6454–6461.
Version
Author's final manuscript
Abstract
Intracellular protein delivery has potential biotechnological and therapeutic application, but remains technically challenging. In contrast, a plethora of nucleic acid carriers have been developed, with lipid-based nanoparticles (LNPs) among the most clinically advanced reagents for oligonucleotide delivery. Here, we validate the hypothesis that oligonucleotides can serve as packaging materials to facilitate protein entrapment within and intracellular delivery by LNPs. Using two distinct model proteins, horseradish peroxidase and NeutrAvidin, we demonstrate that LNPs can yield efficient intracellular protein delivery in vitro when one or more oligonucleotides have been conjugated to the protein cargo. Moreover, in experiments with NeutrAvidin in vivo, we show that oligonucleotide conjugation significantly enhances LNP-mediated protein uptake within various spleen cell populations, suggesting that this approach may be particularly suitable for improved delivery of protein-based vaccines to antigen-presenting cells.
MIT 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 Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.biomaterials.2014.04.014
