Development of Next-Generation mRNA Nanomedicine

Messenger RNA (mRNA) nanomedicine is transforming the treatment of genetic disorders, cancer, and infectious diseases by enabling precise gene modulation, therapeutic protein expression, and immune activation. However, its clinical success depends on overcoming delivery, stability, and tissue-specificity challenges. This seminar will first explore mRNA therapeutics for genetic disorders, focusing on pulmonary RNA delivery for cystic fibrosis. Our lab has developed novel ionizable lipids optimized for inhalable LNPs, enabling adenine base editing for CFTR gene correction. Next, I will discuss mRNA-based cancer immunotherapy, highlighting tumor-customized LNPs that enhance tumor selectivity while minimizing liver off-targeting. These LNPs deliver MLKL-4HB mRNA, inducing immunogenic cell death and improving the response of immunologically “cold” tumors to immune checkpoint inhibitors. Finally, I will introduce our AI-driven platforms for mRNA nanomedicine, including AGILE and LUMI-lab, which integrate deep learning, robotic synthesis, and high-throughput screening to optimize LNP design. These platforms have identified novel lipids that outperform clinical benchmarks, advancing RNA therapeutics for gene editing and immunotherapy. By combining AI, synthetic biology, and lipid chemistry, we aim to accelerate the development of next-generation mRNA nanomedicines with broad clinical impact.