This study demonstrates the use of Cas9-packaging enveloped delivery vehicles (Cas9-EDVs) to deliver genome editing tools to specific cells. Cas9-EDVs, which encapsulate CRISPR-Cas9 protein and guide RNA, can be targeted to specific cells using antibody fragments displayed on the particles. This approach allows for selective genome editing in target cells over bystander cells, both ex vivo and in vivo. The study shows that Cas9-EDVs can be used to generate genome-edited chimeric antigen receptor (CAR) T cells in humanized mice, establishing a programmable delivery method with potential therapeutic applications. The optimized Cas9-EDVs maintain receptor-mediated delivery specificity and can be administered systemically, offering advantages over other in vivo delivery methods. The findings highlight the potential of Cas9-EDVs for selective cell editing and complex genome engineering in human immune cells.This study demonstrates the use of Cas9-packaging enveloped delivery vehicles (Cas9-EDVs) to deliver genome editing tools to specific cells. Cas9-EDVs, which encapsulate CRISPR-Cas9 protein and guide RNA, can be targeted to specific cells using antibody fragments displayed on the particles. This approach allows for selective genome editing in target cells over bystander cells, both ex vivo and in vivo. The study shows that Cas9-EDVs can be used to generate genome-edited chimeric antigen receptor (CAR) T cells in humanized mice, establishing a programmable delivery method with potential therapeutic applications. The optimized Cas9-EDVs maintain receptor-mediated delivery specificity and can be administered systemically, offering advantages over other in vivo delivery methods. The findings highlight the potential of Cas9-EDVs for selective cell editing and complex genome engineering in human immune cells.