In vivo engineering of CAR natural killer cells for immunotherapy using ligand-directed lipid nanoparticles.

Ligand-directed lipid nanoparticles achieve up to 80% in vivo transfection of NK cells and enable effective CAR NK cell generation in mice.

• Why it matters: Efficient in vivo programming of natural killer cells remains limited, hindering the development of nonviral immunotherapies for cancer and autoimmune diseases.
• What they did: Researchers developed NK cell-targeted lipid nanoparticles using engineered biparatopic ligands, delivering CAR mRNA systemically to generate CAR NK cells in mice, with high specificity and minimal off-target effects.
• The result: The approach led to complete B cell depletion and near-total autoreactive T cell elimination in mice, improved antitumor responses in solid tumors, and enabled regression of human hematologic malignancies, supporting NtLNPs as a versatile immunotherapy platform.