MasterSwitch Bio has received a USD 1.19 million SBIR grant from the National Institute of Diabetes and Digestive and Kidney Diseases to advance an HNF4α mRNA therapy for decompensated cirrhosis and end-stage liver disease. The Direct-to-Phase II award will support dose optimization, immunogenicity studies, and manufacturing development intended to prepare the program for an IND filing.
The therapy uses lipid nanoparticles to deliver mRNA encoding hepatocyte nuclear factor 4 alpha (HNF4α), a master regulator of hepatocyte differentiation and liver-specific gene expression. MasterSwitch is developing the approach to restore HNF4α activity in damaged liver tissue, where expression of the transcription factor is reduced in advanced cirrhosis. Preclinical work has shown restoration of HNF4α and downstream hepatocyte proteins in human liver-cell models.
MasterSwitch Bio is a joint spinout of the University of Pittsburgh and the University of Pennsylvania and was co-founded by 2023 Nobel laureate Drew Weissman, whose work underpins the company’s modified mRNA technology. The company is developing transcription factor mRNA therapies aimed at restoring organ function, with HNF4α replacement in end-stage liver disease as its lead program.
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