Technologies for chimeric antigen receptor transgene delivery
- Trends Mol Med. 2025 Nov;31(11):1047-1064. doi: 10.1016/j.molmed.2025.05.011.
- 1. Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
- 2. Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
- 3. Key Laboratory of Multi-Cell Systems, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
- 4. Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China. Electronic address: [email protected].
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.