Engineering nanotechnology for in vivo CAR cell therapy

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of B cell malignancies over the past decades. Despite its success, CAR-T cell therapy remains limited by high costs, complex ex vivo manufacturing, and the risk of severe adverse effects. In vivo generation of CAR-T cells is emerging as a promising alternative, offering a less invasive, off-the-shelf approach that streamlines production while reducing logistical and financial burdens. To enable the delivery of CAR-encoding nucleic acids to immune cells, a range of delivery platforms is being explored, including non-viral lipid and polymeric nanoparticles as well as viral vectors based on lentiviruses and adeno-associated viruses (AAVs). Among these, lipid nanoparticles (LNPs) encapsulating mRNA present distinct advantages: they enable scalable, standardized manufacturing–exemplified by the rapid development of COVID-19 mRNA vaccines—and offer improved cost–effectiveness and accessibility. This commentary highlights the current landscape of in vivo CAR-T cell therapy and discusses key bioengineering strategies for the successful implementation of LNP-mRNA platforms.