Fibroblast growth factor 21 (FGF21) messenger RNA (FGF21 mRNA)

Fibroblast growth factor 21 (FGF21) messenger RNA (mRNA) is a therapeutic modality designed to induce the endogenous synthesis of the FGF21 protein, a potent metabolic regulator (UniProt: Q9NSA1). FGF21 acts as an endocrine hormone that improves insulin sensitivity, reduces hepatic fat, and modulates lipid metabolism by signaling through the FGFR1c/beta-Klotho receptor complex (PubMed: 30510249). In the context of metabolic dysfunction-associated steatohepatitis (MASH) and obesity, FGF21 mRNA is delivered via lipid nanoparticles to the liver to compensate for metabolic deficiencies or to provide supra-physiological levels of the hormone for therapeutic benefit. This approach offers advantages over recombinant proteins, such as more natural post-translational modifications and potentially more favorable pharmacokinetics (ClinicalTrials.gov: NCT04834817). Clinical candidates like BNT191 have explored this mechanism to reduce liver fat and inflammation in patients with chronic liver disease. The success of this target depends on efficient hepatic delivery and the management of immune responses to the delivery vehicle. By leveraging the host's cellular machinery, FGF21 mRNA therapy aims to provide a sustained metabolic effect that can reverse the progression of fatty liver disease and improve systemic glucose control.

Other names

FGF-21 mRNAFibroblast growth factor 21 transcriptFGF21 transcript

Translation of exogenous mRNA into functional Fibroblast growth factor 21 protein, which acts as an endocrine hormone to regulate metabolic pathways.