Novel Molecular Targeted Nucleic Acid Therapy for Liver Fibrosis

This project will aim to develop an innovative antisense nucleic acid therapy targeting a novel intracellular adaptor molecule that regulates extracellular matrix (ECM) dynamics and tissue stiffness in the liver. This adaptor molecule is important for controlling hepatic stellate cell activation and abnormal ECM deposition. This adaptor has historically been considered “undruggable” by conventional small molecules or antibodies because of its structural and functional properties. By leveraging nucleic acid medicine, we can selectively and efficiently suppress the expression of this molecule, enabling direct therapeutic intervention for the first time.

Liver fibrosis, characterized by excessive ECM accumulation from chronic inflammation or injury, often progresses to cirrhosis, liver failure, or cancer, and currently lacks therapies that directly reverse fibrosis. Our approach will not only inhibit the progression of fibrosis but also promote the resolution of established fibrotic tissue by deactivating activated hepatic stellate cells, aiming for true reversal of liver fibrosis.

Importantly, this adaptor molecule is also involved in fibrotic processes in other organs and in the regulation of the tumor stroma in solid cancers. Therefore, while our initial focus will be on liver fibrosis, the therapeutic platform that will be established through this research is promising for broader applications, such as the treatment of fibrosis in other organs and modulation of the tumor microenvironment in solid tumors. Ultimately, this project seeks to pioneer a new paradigm in molecular targeted therapy for fibrosis and cancer, contributing to healthy longevity and improved quality of life.