Cell type-specific delivery by modular envelope design
Abstract The delivery of genetic cargo remains one of the largest obstacles to the successful translation of experimental therapies, in large part due to the absence of targetable delivery vectors. Enveloped delivery modalities use viral envelope proteins, which determine tropism and induce membrane...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40788-8 |
| _version_ | 1797558805727281152 |
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| author | Daniel Strebinger Chris J. Frangieh Mirco J. Friedrich Guilhem Faure Rhiannon K. Macrae Feng Zhang |
| author_facet | Daniel Strebinger Chris J. Frangieh Mirco J. Friedrich Guilhem Faure Rhiannon K. Macrae Feng Zhang |
| author_sort | Daniel Strebinger |
| collection | DOAJ |
| description | Abstract The delivery of genetic cargo remains one of the largest obstacles to the successful translation of experimental therapies, in large part due to the absence of targetable delivery vectors. Enveloped delivery modalities use viral envelope proteins, which determine tropism and induce membrane fusion. Here we develop DIRECTED (Delivery to Intended REcipient Cells Through Envelope Design), a modular platform that consists of separate fusion and targeting components. To achieve high modularity and programmable cell type specificity, we develop multiple strategies to recruit or immobilize antibodies on the viral envelope, including a chimeric antibody binding protein and a SNAP-tag enabling the use of antibodies or other proteins as targeting molecules. Moreover, we show that fusogens from multiple viral families are compatible with DIRECTED and that DIRECTED components can target multiple delivery chassis (e.g., lentivirus and MMLV gag) to specific cell types, including primary human T cells in PBMCs and whole blood. |
| first_indexed | 2024-03-10T17:35:31Z |
| format | Article |
| id | doaj.art-6a7ddcde3b644b52a67cbf43c5219c29 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:35:31Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-6a7ddcde3b644b52a67cbf43c5219c292023-11-20T09:51:37ZengNature PortfolioNature Communications2041-17232023-08-0114111810.1038/s41467-023-40788-8Cell type-specific delivery by modular envelope designDaniel Strebinger0Chris J. Frangieh1Mirco J. Friedrich2Guilhem Faure3Rhiannon K. Macrae4Feng Zhang5Howard Hughes Medical InstituteHoward Hughes Medical InstituteHoward Hughes Medical InstituteHoward Hughes Medical InstituteHoward Hughes Medical InstituteHoward Hughes Medical InstituteAbstract The delivery of genetic cargo remains one of the largest obstacles to the successful translation of experimental therapies, in large part due to the absence of targetable delivery vectors. Enveloped delivery modalities use viral envelope proteins, which determine tropism and induce membrane fusion. Here we develop DIRECTED (Delivery to Intended REcipient Cells Through Envelope Design), a modular platform that consists of separate fusion and targeting components. To achieve high modularity and programmable cell type specificity, we develop multiple strategies to recruit or immobilize antibodies on the viral envelope, including a chimeric antibody binding protein and a SNAP-tag enabling the use of antibodies or other proteins as targeting molecules. Moreover, we show that fusogens from multiple viral families are compatible with DIRECTED and that DIRECTED components can target multiple delivery chassis (e.g., lentivirus and MMLV gag) to specific cell types, including primary human T cells in PBMCs and whole blood.https://doi.org/10.1038/s41467-023-40788-8 |
| spellingShingle | Daniel Strebinger Chris J. Frangieh Mirco J. Friedrich Guilhem Faure Rhiannon K. Macrae Feng Zhang Cell type-specific delivery by modular envelope design Nature Communications |
| title | Cell type-specific delivery by modular envelope design |
| title_full | Cell type-specific delivery by modular envelope design |
| title_fullStr | Cell type-specific delivery by modular envelope design |
| title_full_unstemmed | Cell type-specific delivery by modular envelope design |
| title_short | Cell type-specific delivery by modular envelope design |
| title_sort | cell type specific delivery by modular envelope design |
| url | https://doi.org/10.1038/s41467-023-40788-8 |
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