Genetically Encoded DNA Origami for CAR-T-Based Immunotherapy.

Abstract

DNA origami has been widely employed in biomedical applications, including bioimaging, biosensing, and drug delivery. However, the gene-encoding capability of the DNA scaffold in DNA origami has rarely been developed. Herein, we introduce a universal strategy to construct genetically encoded DNA origami for CAR-T-based immunotherapy. Two complementary sense and antisense strands encoding the chimeric antigen receptor (CAR) can be easily included as DNA scaffolds in folding DNA origami. After hybridization, genetically encoded DNA origami can function as the template for lipid growth. With decoration of the CD3 antibody targeting T cells, the lipid-coated and genetically encoded DNA origami can efficiently recognize and penetrate the cell membrane of T cells. After targeted cellular uptake, a successful CAR expression can be achieved to capture related tumor cells for CAR-T-based immunotherapy. This rationally developed DNA-origami-based delivery system provides a new avenue for the development of CAR-T therapy.