The paper presents a new delivery system called Cas9-enveloped delivery vehicles (Cas9-EDVs) to target and edit genes in specific human cell types in vivo. Cas9-EDVs are virus-like particles that can package and deliver pre-assembled Cas9 ribonucleoproteins (RNPs) for gene editing. They display both a fusogenic protein (VSVGmut) for cell entry and an antibody-derived single-chain variable fragment (scFv) for cell-specific targeting.
The authors show that Cas9-EDVs can selectively edit genes in target cells expressing the cognate surface receptor, with minimal off-target editing of bystander cells lacking that receptor. Optimization of the Cas9-EDV system enhanced editing efficiency in both cell lines and primary human cells. Using multiple scFvs, Cas9-EDVs enabled editing of specific immune cell subsets like T cells.