PhD Student The University of Hong Kong, Hong Kong
Abstract: Cardiac fibrosis is a major driver of heart failure progression, yet therapeutic options remain limited. Signal transducer and activator of transcription 3 (STAT3), a key transcription factor, plays a pivotal role in fibrosis by promoting fibroblast activation and extracellular matrix deposition. In this study, we explore the use of base editing, a precise genome-editing technology, to introduce targeted mutations in the STAT3 gene, aiming to disrupt its pro-fibrotic functions. We have established an in vitro model using fibroblasts cell lines treated with TGF-β1 to induce fibrotic differentiation. Using a lentiviral vector, we delivered a cytosine base editor targeting the STAT3 gene to these cells. Preliminary data show reduced expression of fibrosis markers (α-SMA and collagen I) in edited cells compared to controls. Building on these findings, future work will employ stem cell-derived cardiac organoids to model fibrosis in a 3D multicellular system that recapitulates human cardiac pathophysiology.
Leveraging high-throughput base editing screening, we aimed to identify specific STAT3 mutations that effectively inhibit fibrotic pathways in cardiac fibroblasts and develop a precision therapy that not only halts fibrosis progression but also preserves cardiac function.
