Programming T cells for intercellular genome editing

Abstract

Therapeutic genome editing requires delivery of editing molecules to defined cell types, but targeting specificity and efficiency are currently limited. We hypothesized that properties inherent to immune cells, including tissue infiltration and programmed cell recognition, could be harnessed to engineer a cell-based delivery system. We show here that T cells can both produce and transfer editing machinery to target cells. In response to a programmable ligand, engineered T-lymphoid cells can transfer enzymes using complex spatiotemporal logic and deliver cargo in a cell contact-dependent or -independent manner. We demonstrate feasibility of this approach in primary human T cells, establishing a customizable genetic circuit for macromolecular delivery controlled by intercellular interactions.