Technologies for chimeric antigen receptor transgene delivery

Ex vivo chimeric antigen receptor (CAR) T cell therapy has achieved clinical success in hematological malignancies; yet, viral transduction risks insertional mutagenesis. Developing safe and efficient nonviral approaches for the genetic engineering of T cells and other immune cells is the key to next-generation immunotherapy for cancer and noncancerous diseases. mRNA is an emerging modality for CAR engineering because of its transient expression and minimal risks. As a clinically validated nonviral vector, lipid nanoparticles (LNPs) are gaining popularity for ex vivo/in vivo mRNA-based CAR engineering of immune cells, making cell therapy safer and affordable. This review discusses the progress, delivery approaches, and challenges of CAR therapy and highlights mRNA-LNP advancements in shaping future CAR immune cell therapy for oncology and non-oncology.