Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism
Abstract The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development of prophylactic and therapeutic vaccines, immunotherapies for cancer and strategies for genome editing. While polymers an...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42672-x |
| _version_ | 1797636833757102080 |
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| author | Zhijian Li Laura Amaya Ruoxi Pi Sean K. Wang Alok Ranjan Robert M. Waymouth Catherine A. Blish Howard Y. Chang Paul A. Wender |
| author_facet | Zhijian Li Laura Amaya Ruoxi Pi Sean K. Wang Alok Ranjan Robert M. Waymouth Catherine A. Blish Howard Y. Chang Paul A. Wender |
| author_sort | Zhijian Li |
| collection | DOAJ |
| description | Abstract The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development of prophylactic and therapeutic vaccines, immunotherapies for cancer and strategies for genome editing. While polymers and oligomers have served as promising mRNA delivery systems, their efficacy in hard-to-transfect cells such as primary T lymphocytes is often limited as is their cell and organ tropism. To address these problems, considerable attention has been placed on structural screening of various lipid and cation components of mRNA delivery systems. Here, we disclose a class of charge-altering releasable transporters (CARTs) that differ from previous CARTs based on their beta-amido carbonate backbone (bAC) and side chain spacing. These bAC-CARTs exhibit enhanced mRNA transfection in primary T lymphocytes in vitro and enhanced protein expression in vivo with highly selective spleen tropism, supporting their broader therapeutic use as effective polyanionic delivery systems. |
| first_indexed | 2024-03-11T12:39:49Z |
| format | Article |
| id | doaj.art-9e61f17a635449b78342282fbc40e058 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T12:39:49Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-9e61f17a635449b78342282fbc40e0582023-11-05T12:22:22ZengNature PortfolioNature Communications2041-17232023-11-0114111510.1038/s41467-023-42672-xCharge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropismZhijian Li0Laura Amaya1Ruoxi Pi2Sean K. Wang3Alok Ranjan4Robert M. Waymouth5Catherine A. Blish6Howard Y. Chang7Paul A. Wender8Department of Chemistry, Stanford UniversityCenter for Personal Dynamic Regulomes, Stanford UniversityDivision of Infectious Diseases and Geographic Medicine, Department of MedicineCenter for Personal Dynamic Regulomes, Stanford UniversityDepartment of Chemistry, Stanford UniversityDepartment of Chemistry, Stanford UniversityDivision of Infectious Diseases and Geographic Medicine, Department of MedicineCenter for Personal Dynamic Regulomes, Stanford UniversityDepartment of Chemistry, Stanford UniversityAbstract The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development of prophylactic and therapeutic vaccines, immunotherapies for cancer and strategies for genome editing. While polymers and oligomers have served as promising mRNA delivery systems, their efficacy in hard-to-transfect cells such as primary T lymphocytes is often limited as is their cell and organ tropism. To address these problems, considerable attention has been placed on structural screening of various lipid and cation components of mRNA delivery systems. Here, we disclose a class of charge-altering releasable transporters (CARTs) that differ from previous CARTs based on their beta-amido carbonate backbone (bAC) and side chain spacing. These bAC-CARTs exhibit enhanced mRNA transfection in primary T lymphocytes in vitro and enhanced protein expression in vivo with highly selective spleen tropism, supporting their broader therapeutic use as effective polyanionic delivery systems.https://doi.org/10.1038/s41467-023-42672-x |
| spellingShingle | Zhijian Li Laura Amaya Ruoxi Pi Sean K. Wang Alok Ranjan Robert M. Waymouth Catherine A. Blish Howard Y. Chang Paul A. Wender Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism Nature Communications |
| title | Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism |
| title_full | Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism |
| title_fullStr | Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism |
| title_full_unstemmed | Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism |
| title_short | Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism |
| title_sort | charge altering releasable transporters enhance mrna delivery in vitro and exhibit in vivo tropism |
| url | https://doi.org/10.1038/s41467-023-42672-x |
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