Cell type-specific delivery by modular envelope design.

Autor: Strebinger D; Howard Hughes Medical Institute, Cambridge, MA, 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Frangieh CJ; Howard Hughes Medical Institute, Cambridge, MA, 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Friedrich MJ; Howard Hughes Medical Institute, Cambridge, MA, 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Faure G; Howard Hughes Medical Institute, Cambridge, MA, 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Macrae RK; Howard Hughes Medical Institute, Cambridge, MA, 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Zhang F; Howard Hughes Medical Institute, Cambridge, MA, 02139, USA. zhang@broadinstitute.org.; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. zhang@broadinstitute.org.; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. zhang@broadinstitute.org.; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. zhang@broadinstitute.org.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. zhang@broadinstitute.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Aug 23; Vol. 14 (1), pp. 5141. Date of Electronic Publication: 2023 Aug 23.
DOI: 10.1038/s41467-023-40788-8
Abstrakt: 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: