In vivo human T cell engineering with enveloped delivery vehicles

In vivo human T cell engineering with enveloped delivery vehicles

11 January 2024 | Jennifer R. Hamilton, Evelyn Chen, Barbara S. Perez, Cindy R. Sandoval Espinoza, Min Hyung Kang, Marena Trinidad, Wayne Ngo & Jennifer A. Doudna
This study presents a novel method for in vivo delivery of genome editing tools using Cas9-packaging enveloped delivery vehicles (Cas9-EDVs). These vehicles use antibody-targeted surface markers to deliver CRISPR-Cas9 and guide RNA to specific cells, enabling precise genome editing. Unlike conventional vectors such as adeno-associated virus, Cas9-EDVs leverage predictable antibody-antigen interactions for targeted delivery. The study demonstrates that Cas9-EDVs can efficiently edit genes in specific cell types, both in vitro and in vivo, with minimal off-target effects. The technology was tested in humanized mice, where it successfully generated genome-edited chimeric antigen receptor (CAR) T cells, showing potential for therapeutic applications. The study also highlights the ability of Cas9-EDVs to deliver molecular cargo to specific cells in the body, offering a programmable platform for complex genome engineering. The results suggest that Cas9-EDVs could be a valuable tool for in vivo genome editing, with potential applications in cancer treatment and other diseases. The study also discusses the advantages of Cas9-EDVs over other delivery methods, including their ability to deliver multiple cargo molecules and their potential for reducing off-target effects. The research provides a promising approach for targeted genome editing in vivo, with potential for widespread therapeutic use.This study presents a novel method for in vivo delivery of genome editing tools using Cas9-packaging enveloped delivery vehicles (Cas9-EDVs). These vehicles use antibody-targeted surface markers to deliver CRISPR-Cas9 and guide RNA to specific cells, enabling precise genome editing. Unlike conventional vectors such as adeno-associated virus, Cas9-EDVs leverage predictable antibody-antigen interactions for targeted delivery. The study demonstrates that Cas9-EDVs can efficiently edit genes in specific cell types, both in vitro and in vivo, with minimal off-target effects. The technology was tested in humanized mice, where it successfully generated genome-edited chimeric antigen receptor (CAR) T cells, showing potential for therapeutic applications. The study also highlights the ability of Cas9-EDVs to deliver molecular cargo to specific cells in the body, offering a programmable platform for complex genome engineering. The results suggest that Cas9-EDVs could be a valuable tool for in vivo genome editing, with potential applications in cancer treatment and other diseases. The study also discusses the advantages of Cas9-EDVs over other delivery methods, including their ability to deliver multiple cargo molecules and their potential for reducing off-target effects. The research provides a promising approach for targeted genome editing in vivo, with potential for widespread therapeutic use.
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[slides and audio] In vivo human T cell engineering with enveloped delivery vehicles