Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery
Messenger RNA (mRNA) represents a promising class of nucleic acid drugs. Although numerous carriers have been developed for mRNA delivery, the inefficient mRNA expression inside cells remains a major challenge. Inspired by the dependence of mRNA on 3′-terminal polyadenosine nucleotides (poly A) and...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019
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| Online Access: | https://hdl.handle.net/1721.1/122816 |
| _version_ | 1811082708986626048 |
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| author | Li, Jiahe He, Yanpu Wang, Wade Wu, Connie Hong, Celestine Hammond, Paula T |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Li, Jiahe He, Yanpu Wang, Wade Wu, Connie Hong, Celestine Hammond, Paula T |
| author_sort | Li, Jiahe |
| collection | MIT |
| description | Messenger RNA (mRNA) represents a promising class of nucleic acid drugs. Although numerous carriers have been developed for mRNA delivery, the inefficient mRNA expression inside cells remains a major challenge. Inspired by the dependence of mRNA on 3′-terminal polyadenosine nucleotides (poly A) and poly A binding proteins (PABPs) for optimal expression, we complexed synthetic mRNA containing a poly A tail with PABPs in a stoichiometric manner and stabilized the ribonucleoproteins (RNPs) with a family of polypeptides bearing different arrangements of cationic side groups. We found that the molecular structure of these polypeptides modulates the degree of PABP-mediated enhancement of mRNA expression. This strategy elicits an up to 20-fold increase in mRNA expression in vitro and an approximately fourfold increase in mice. These findings suggest a set of new design principles for gene delivery by the synergistic co-assembly of mRNA with helper proteins. |
| first_indexed | 2024-09-23T12:07:41Z |
| format | Article |
| id | mit-1721.1/122816 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:07:41Z |
| publishDate | 2019 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1228162022-09-28T00:21:11Z Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery Li, Jiahe He, Yanpu Wang, Wade Wu, Connie Hong, Celestine Hammond, Paula T Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Koch Institute for Integrative Cancer Research at MIT Messenger RNA (mRNA) represents a promising class of nucleic acid drugs. Although numerous carriers have been developed for mRNA delivery, the inefficient mRNA expression inside cells remains a major challenge. Inspired by the dependence of mRNA on 3′-terminal polyadenosine nucleotides (poly A) and poly A binding proteins (PABPs) for optimal expression, we complexed synthetic mRNA containing a poly A tail with PABPs in a stoichiometric manner and stabilized the ribonucleoproteins (RNPs) with a family of polypeptides bearing different arrangements of cationic side groups. We found that the molecular structure of these polypeptides modulates the degree of PABP-mediated enhancement of mRNA expression. This strategy elicits an up to 20-fold increase in mRNA expression in vitro and an approximately fourfold increase in mice. These findings suggest a set of new design principles for gene delivery by the synergistic co-assembly of mRNA with helper proteins. United States. Department of Defense. Ovarian Cancer Research Program. United States. Department of Defense. Peer Reviewed Orthopaedic Research Program. 2019-11-11T17:14:34Z 2019-11-11T17:14:34Z 2017-09 2019-08-20T17:30:56Z Article http://purl.org/eprint/type/JournalArticle 1433-7851 https://hdl.handle.net/1721.1/122816 Li, Jiahe et al. "Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery." Angewandte Chemie (International ed. in English) 56, 44 (October 2017) : 13709–13712 © 2017 Publisher en http://dx.doi.org/10.1002/anie.201707466 Angewandte Chemie (International ed. in English) Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley PMC |
| spellingShingle | Li, Jiahe He, Yanpu Wang, Wade Wu, Connie Hong, Celestine Hammond, Paula T Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery |
| title | Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery |
| title_full | Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery |
| title_fullStr | Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery |
| title_full_unstemmed | Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery |
| title_short | Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery |
| title_sort | polyamine mediated stoichiometric assembly of ribonucleoproteins for enhanced mrna delivery |
| url | https://hdl.handle.net/1721.1/122816 |
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