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Cell type-programmable genome editing with enveloped delivery vehicles

Hamilton, J. R.; Chen, E.; Perez, B. S.; Sandoval Espinoza, C. R.; Doudna, J. A.

2022-08-24 genomics
10.1101/2022.08.24.505004 bioRxiv
Show abstract

Viruses and virally-derived particles have the intrinsic capacity to deliver molecules to cells, but the difficulty of readily altering cell-type selectivity has hindered their use for therapeutic delivery. Here we show that cell surface marker recognition by antibody fragments displayed on membrane-derived particles encapsulating CRISPR-Cas9 protein and guide RNA can target genome editing tools to specific cells. These Cas9-packaging enveloped delivery vehicles (Cas9-EDVs), programmed with different displayed antibody fragments, confer genome editing in target cells over bystander cells in mixed cell populations both ex vivo and in vivo. This strategy enabled the generation of genome-edited chimeric antigen receptor (CAR) T cells in humanized mice, establishing a new programmable delivery modality with widespread therapeutic utility. One-Sentence SummaryCell-specific molecular delivery with enveloped delivery vehicles (EDVs) enables genome editing ex vivo and in vivo.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.