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Genetically encoding multiple functionalities into extracellular vesicles for the targeted delivery of biologics to T cells
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Genetically encoding multiple functionalities into extracellular vesicles for the targeted delivery of biologics to T cells
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Journal Article
Genetically encoding multiple functionalities into extracellular vesicles for the targeted delivery of biologics to T cells
2024
Overview
The genetic modification of T cells has advanced cellular immunotherapies, yet the delivery of biologics specifically to T cells remains challenging. Here we report a suite of methods for the genetic engineering of cells to produce extracellular vesicles (EVs)—which naturally encapsulate and transfer proteins and nucleic acids between cells—for the targeted delivery of biologics to T cells without the need for chemical modifications. Specifically, the engineered cells secreted EVs that actively loaded protein cargo via a protein tag and that displayed high-affinity T-cell-targeting domains and fusogenic glycoproteins. We validated the methods by engineering EVs that delivered Cas9–single-guide-RNA complexes to ablate the gene encoding the C-X-C chemokine co-receptor type 4 in primary human CD4
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T cells. The strategy is amenable to the targeted delivery of biologics to other cell types.
Biologics can be specifically delivered to T cells by genetically engineering cells to secrete extracellular vesicles that actively load protein cargo and that display high-affinity T-cell-targeting domains and fusogenic glycoproteins.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Ablation
/ Affinity
/ Biomedical and Life Sciences
/ Biomedical Engineering/Biotechnology
/ Cargo
/ CD4-Positive T-Lymphocytes - metabolism
/ CRISPR-Cas Systems - genetics
/ Drug Delivery Systems - methods
/ Extracellular Vesicles - metabolism
/ Genetic Engineering - methods
/ Humans
/ Proteins
/ Vesicles
