Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles
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...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/110153 https://orcid.org/0000-0001-6898-3793 https://orcid.org/0000-0001-5786-0659 https://orcid.org/0000-0001-5629-4798 |
| _version_ | 1826199364144463872 |
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| author | Chen, Delai Veiseh, Omid Pelet, Jeisa Yin, Hao Dong, Yizhou Anderson, Daniel Griffith Eltoukhy, Ahmed A. |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Chen, Delai Veiseh, Omid Pelet, Jeisa Yin, Hao Dong, Yizhou Anderson, Daniel Griffith Eltoukhy, Ahmed A. |
| author_sort | Chen, Delai |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:18:43Z |
| format | Article |
| id | mit-1721.1/110153 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:18:43Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1101532022-09-27T18:39:59Z Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles Chen, Delai Veiseh, Omid Pelet, Jeisa Yin, Hao Dong, Yizhou Anderson, Daniel Griffith Eltoukhy, Ahmed A. 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 Eltoukhy, Ahmed Atef Chen, Delai Veiseh, Omid Pelet, Jeisa Yin, Hao Dong, Yizhou Anderson, Daniel Griffith 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. National Heart, Lung, and Blood Institute (Contract HHSN268201000045C) National Institutes of Health (U.S.) (Grant R01-EB000244-27) National Institutes of Health (U.S.) (Grant 5-R01-CA132091-04) National Science Foundation (U.S.) Juvenile Diabetes Research Foundation International (Grant 17–2007-1063) United States. Dept. of Defense. Congressionally Directed Medical Research Programs (Grant W81XWH-13-1-0215) 2017-06-21T19:57:14Z 2017-06-21T19:57:14Z 2014-05 2014-02 Article http://purl.org/eprint/type/JournalArticle http://hdl.handle.net/1721.1/110153 Eltoukhy, Ahmed A. et al. “Nucleic Acid-Mediated Intracellular Protein Delivery by Lipid-like Nanoparticles.” Biomaterials 35.24 (2014): 6454–6461. https://orcid.org/0000-0001-6898-3793 https://orcid.org/0000-0001-5786-0659 https://orcid.org/0000-0001-5629-4798 en_US http://dx.doi.org/10.1016/j.biomaterials.2014.04.014 Biomaterials Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Chen, Delai Veiseh, Omid Pelet, Jeisa Yin, Hao Dong, Yizhou Anderson, Daniel Griffith Eltoukhy, Ahmed A. Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles |
| title | Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles |
| title_full | Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles |
| title_fullStr | Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles |
| title_full_unstemmed | Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles |
| title_short | Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles |
| title_sort | nucleic acid mediated intracellular protein delivery by lipid like nanoparticles |
| url | http://hdl.handle.net/1721.1/110153 https://orcid.org/0000-0001-6898-3793 https://orcid.org/0000-0001-5786-0659 https://orcid.org/0000-0001-5629-4798 |
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