mRNA Therapy to Prevent Liver Disease Progression in Zellweger Spectrum Disorder

Zellweger Spectrum Disorder (ZSD) is a rare genetic disorder causing multisystemic complications affecting growth, vision and hearing, brain and liver. Most patients harbor mutations in PEX1 gene and suffer from chronic liver disease which may progress to hepatic cancer. Therefore, restoring PEX1 function may improve disease outcome and benefit most patients. We hypothesize that liver disease in ZSD can be prevented or alleviated by PEX1 mRNA therapy. We will use lipid nanoparticles to deliver mRNA encoding functional PEX1 into our mouse model and evaluate its therapeutic effects. Our research will enable the development of the first RNA therapy for ZSD.