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Cell type-specific delivery by modular envelope design.

Daniel StrebingerChris J FrangiehMirco J FriedrichGuilhem FaureRhiannon K MacraeFeng Zhang
Published in: Nature communications (2023)
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.
Keyphrases
  • sars cov
  • binding protein
  • endothelial cells
  • cell therapy
  • stem cells
  • induced apoptosis
  • gene expression
  • single cell
  • high throughput
  • dna methylation
  • oxidative stress
  • genome wide
  • signaling pathway
  • cell death
  • copy number