Wenjun "Tia" Li, on Reducing Swelling in Mouse Models of Rheumatoid Arthritis With Gene Therapy

“We found that AAV5/PD-L1 could significantly decrease the inflammation in the knee joints based on the T-cell macrophage infiltration, as well as the cytokine levels in the local area. And we didn't see any significant changes in the systematic condition, the mouse all stayed the same as the control group. AAV particles were highly present in the knee joints and there's no significant side effects. So, I think it's very promising.”

Researchers from University of North Carolina (UNC) – Chapel Hill investigated AAV5/PD-L1 gene therapy in preclinical studies in mouse models of rheumatoid arthritis (RA). The preclinical data were presented at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California, by Wenujun "Tia" Li, PhD candidate, UNC Chapel Hill.

CGTLive spoke with Li to learn more about the preclinical data and the rationale for the research. She discussed the unmet need in patients with RA and how gene therapy has the potential to improve outcomes in this population. She outlined some notable findings from her research, including a significant reduction in swelling in mice treated with 5 x 10⁹ vg AAV5/PD-L1 and lower histopathological scores compared to the control mice injected with AAV5/luc vectors. She stressed that despite the high AAV expression in knee joints and efficacy in reducing swelling, no significant adverse events were observed. These findings were strengthened with the use of an AAV5/shPD-L1 gene therapy. She also discussed further research she’d like to pursue with gene therapy for RA, including investigating an AAV6 vector instead of AAV5.

Click here to read more coverage of the ASGCT 2023 meeting.

REFERENCE

Li W, Sun J, Feng SL, et al. Intra-Articular Delivery of AAV Vectors Encoding Immune Checkpoint Protein as a Novel Treatment for Arthritis. Presented at: ASGCT 2023 Annual Meeting. Abstract #136