A cyclic peptide-grafted Fc with hepatocyte growth factor functionality ameliorates hepatic fibrosis in a non-alcoholic steatohepatitis mouse model.

ABSTRACT: The regenerative functions associated with cytokines and growth factors have immense therapeutic potential; however, their poor pharmacokinetics, resulting from structural features, hinder their effectiveness. In this study, we aimed to enhance the pharmacokinetics of growth factors by designing receptor-binding macrocyclic peptides through in vitro mRNA display and grafting them into loops of immunoglobulin's crystallizable region (Fc). As a model, we developed peptide-grafted Fc proteins with hepatocyte growth factor (HGF) functionality that exhibited a prolonged circulation half-life and could be administered subcutaneously. The Fc-based HGF mimetic alleviated liver fibrosis in a mouse model fed a choline-deficient high-fat diet, which induces hepatic features of non-alcoholic st

SUBMITTER: Rojas-Chaverra NM 

PROVIDER: S-EPMC11300919 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature