Grant: Fellowship: Canada Impact+ Research Training Awards - Postdoctoral

"Self-amplifying RNA (saRNA) is an emerging RNA technology with strong potential for treating cancer and other serious diseases. Unlike conventional mRNA, saRNA can copy itself inside cells, allowing higher and longer-lasting production of therapeutic proteins while requiring much lower doses. This makes saRNA a highly attractive platform for cancer therapy, where sustained activity and efficient delivery are essential. However, a major challenge is that cells often recognize saRNA as a viral signal and activate innate immune defenses that shut down its activity, reducing effectiveness and limiting its safe clinical use. The goal of this research is to improve the performance of saRNA-based cancer therapies by understanding and precisely controlling these immune reactions. The project will investigate how different saRNA designs trigger immune responses in both cancer and normal cells, and how these responses influence RNA stability, protein production, and cell survival. By analyzing changes in gene activity and RNA processing over time, the study will identify key immune pathways that restrict saRNA persistence and therapeutic output. Based on these findings, targeted strategies will be tested to temporarily reduce harmful immune responses using small-molecule drugs and gene-silencing approaches, while preserving beneficial immune functions. A central focus is to enhance saRNA activity specifically in cancer cells, improving durability and effectiveness without increasing toxicity to healthy tissues. Ultimately, this research aims to advance safer and more effective RNA-based cancer treatments and contribute to the development of next-generation RNA medicines with strong potential for clinical translation and meaningful patient benefit. "