Area of Research
Nucleic acids, also known as genetic medicines, have been emerging as a promising new class of medicine, which confer tremendous flexibility and broader therapeutic utility than any other known drug. At present, the clinical translation of nucleic acids remains challenging due to their labile nature, insufficient delivery efficiency, and potential side effects. Through a fusion of biomolecular sciences with material engineering, pharmaceutics, and immunology, the Li lab explores new biomaterials and nanoparticles to build safe and effective delivery platforms for nucleic acids. The overall objective of Li lab is to develop novel nucleic acid-based vaccines and therapeutics for a range of human health applications including vaccination, immunotherapy, and regenerative medicine.
Research Challenge
The COVID-19 pandemic catalyzed the most rapid vaccine development in history, with mRNA vaccines at the forefront of those efforts. Although it is now clear that mRNA vaccines can rapidly and safely protect patients from SARS-CoV-2, the clinical translation of RNA in other applications including oncology vaccines, immunotherapy, cellular reprogramming, and genome editing remains challenging due to their labile nature, insufficient delivery efficiency, and the potential side effects. Additional research is required to optimize the design of RNA structures as well as their delivery systems.
Proposed Solution
The Li lab uses nonviral biomaterial-centric approaches to facilitate the development of nucleic acid-based vaccines and therapy, which includes:
- Combinatorial synthesis of novel biomaterials and nanoparticles for the delivery of nucleic acids (siRNA, miRNA, mRNA, CRISPR-Cas9);
- Investigating the influence of biomaterial chemical structure on in vivo transport to target cells and tissues using high-throughput screening platforms;
- Nonviral delivery techniques for in vivo gene editing.
Impact to Date
The Li lab explores new biomaterials and nanoparticles for the safe and effective delivery of nucleic acids including mRNA, circular RNA, siRNA, miRNA and CRISPR-Cas9. In his post-doctoral work, Dr. Li designed a multi-component platform that enables high-throughput synthesis and screening of a combinatorial library of lipid-like materials for mRNA delivery. Using this approach, he identified a series of dual-functional lipid nanoparticles (LNPs) that could not only facilitate efficient mRNA translation in vivo but also actively stimulate immune pathways like an adjuvant. Compared to conventional mRNA LNP vaccines, these immune-stimulating LNPs could better promote antigen presentation and maturation of dendritic cells and thus elicit more robust immune responses for SARS-CoV-2 and oncology vaccination. Moreover, Dr. Li developed tissue-specific lipid materials, whereby a new class of LNPs was discovered to deliver mRNA to target organs, including the liver, spleen, and lung. Co-delivery of Cas9 mRNA/sg RNA using these LNPs could achieve long-term gene editing in therapeutically relevant cell types including lung epithelial cells, immune cells and hepatocytes. These technologies can be applied to better help humans fight infectious diseases, cancer, autoimmunity, and rare diseases.
Notable Awards
- Baxter Young Investigator Award
- Bioengineering Departmental Award for Excellence in Research and Translation
- College of Engineering Student Award for Outstanding Research
Publications
Keywords: mRNA vaccines, cancer immunotherapy, gene editing, Type 1 diabetes, nucleic acid delivery, drug delivery systems, biomaterials, genetic medicines, nanomedicines, immunoengineering, regenerative medicine
