Title: Precision Delivery of Nucleic Acid Medicines: From Engineered RNA to AI-Guided Lipid Nanoparticles
Date and Time: April 22, 2025 | 11 a.m. PST
Location: CHBE 102
Refreshments will be served at 10:50am
Abstract
Nucleic acid therapeutics are revolutionizing medicine, yet their clinical impact remains constrained by the challenge of targeted delivery beyond the liver. In this seminar, I will present our lab’s integrated approach to overcoming this barrier through the development of next-generation lipid nanoparticles (LNPs) for the tissue- and cell-specific delivery of diverse nucleic acid cargos including messenger RNA (mRNA), transfer RNA (tRNA), and gene editors. Our platform enables in vivo delivery to diverse tissues including lung, muscle, and tumor expanding therapeutic opportunities for cancer, cystic fibrosis, Duchenne muscular dystrophy, and hemophilia. We begin by exploring the rational design of lipid-based nanocarriers that are tailored to the distinct biological and physicochemical barriers of target tissues. These efforts have enabled efficient, functional RNA delivery to pulmonary epithelium, skeletal muscle fibers, and tumor-infiltrating immune cells. I will also discuss our strategies for engineering programmable mRNA sequences and chemically stabilized tRNAs to enhance expression, minimize immunogenicity, and improve therapeutic index in vivo. Finally, I will introduce our AI-driven platforms, including the LUMI-lab framework, which integrates unsupervised molecular pretraining, structure–function modeling, and autonomous screening to design and optimize ionizable lipids that support potent mRNA delivery and CRISPR-based gene editing. Together, this talk will demonstrate how synthetic chemistry, biomolecular engineering, and machine learning can converge to advance the next generation of RNA therapeutics that are programmable, safe, and precisely targeted for clinical translation.
Biography
Bowen Li is an Assistant Professor and GSK Chair in Pharmaceutics and Drug Delivery at the Leslie Dan Faculty of Pharmacy, University of Toronto, and an Affiliate Scientist at the Princess Margaret Cancer Centre. He holds the Tier 2 Canada Research Chair in RNA Vaccines and Therapeutics. Dr. Li received his Ph.D. in Bioengineering from the University of Washington, Seattle, and then completed a Postdoc Fellowship under the guidance of Profs. Robert Langer and Daniel Anderson at MIT. His lab utilizes a range of interdisciplinary strategies, including combinatorial chemistry, high throughput platforms, and AI-driven design of experiments, to develop new generations of delivery systems for RNA medicines including mRNA, circRNA, tRNA, and CRISPR. His work has led to over 60 publications in top-tier journals, such as Nat. Biotechnology, Nat. Materials, Nat. Biomedical Engineering, Nat. Medicine, PNAS, Sci. Adv., among others, as well as ten patents. Dr. Li is a recipient of National Sanitarium Association Scholar Award (2025), Oxford-Harrington Rare Disease Scholar Award (2024), NIH R01 grant (2024), CIHR project grants (2022, 2023, 2024), AAPS Emerging Leader Award (2024), CSPS Early Career Award (2024), Marsha Morton Early Career Investigator Award (2024), Biomaterials Science Emerging Investigator Award (2024), Gairdner Early Career Investigator Award (2022), and Connaught New Researcher Award (2022).