RNA Innovation Seminar: Guizhi (Julian) Zhu, University of Michigan

“Engineer and deliver nucleic acid immunotherapeutics and vaccines – a focus on small circular mRNA (circRNA) vaccines”
Guizhi (Julian) Zhu, Ph.D.

Ara G. Paul Associate Professor of Pharmaceutical Science
University of Michigan

In-person: BSRB, ABC Seminar Rooms / hybrid link

Abstract: Our ultimate research goal is to develop clinically translatable nucleic acid therapeutics and vaccines, along with their delivery systems. In this talk, we will mainly discuss small circular mRNA (circRNA) vaccines for cancer immunotherapy and the prevention of infectious diseases. Modification-free small circRNA vaccines are highly stable and sequence-defined with unique innate immunomodulatory mechanisms and sustained production of concatemeric antigens, resulting in robust and long-lasting adaptive immunity. Relative to several state-of-the-art modified mRNAs, nanocarrier-delivered circRNA vaccines elicited up to 10-fold antigen-specific T cells in mice, with superior T cell memory and vaccine safety. circRNA vaccines are widely applicable for tumor and viral (neo)antigens to elicit potent and long-lasting CD8+/CD4+ T cell responses in young or immunosenescent aged mice. Combining circRNA vaccines with immune checkpoint blockade (ICB) reduced tumor immunosuppression and eradicated multiple types of murine tumors, including ICB-resistant BrafV600E melanoma. Moreover, pulmonary delivery of influenza circRNA vaccines protected mice from influenza challenge. Overall, small circRNA vaccines are promising for versatile applications. Lastly, we will also briefly discuss our research in cGAS-STING- and ADAR1- related nucleic acid therapeutics and drug delivery systems for cancer and autoimmune diseases.