MIT researchers have developed lipid nanoparticle–based delivery that reprograms natural killer (NK) cells with chimeric antigen receptor (CAR) constructs directly inside the body, eliminating the need for extraction and ex vivo engineering.

The nanoparticles deliver mRNA encoding CARs and are guided to NK cells by antibody fragments on the particle surface, enabling in vivo NK cell engineering.

This approach could reduce manufacturing challenges and costs tied to CAR T-cell therapies and may extend to autoimmune diseases driven by dysfunctional T cells, such as multiple sclerosis and rheumatoid arthritis.

In a mouse model of autoimmune hepatitis, the strategy allowed NK cells to attack autoreactive T cells, with a single injection destroying these T cells and healing liver damage.

In mouse studies, about 80% of targeted NK cells were reprogrammed, achieving tumor clearance in a humanized mouse model of T-cell lymphoma, akin to conventional CAR NK-cell therapy.

In a melanoma mouse model, most treated mice experienced complete remission after NK cells were reprogrammed to recognize cancer cells.

The study, published in Nature Biotechnology on October 13, 2026, was funded by Sanofi, the Marble Center for Cancer Nanomedicine, and a Koch Institute core grant from the National Cancer Institute.

The research was conducted with support from the Marble Center for Cancer Nanomedicine and funded in part by a Koch Institute core grant from the National Cancer Institute.