Targeted Therapy of Osteoarthritis via Intra-Articular Delivery of Lipid-Nanoparticle-Encapsulated Recombinant Human FGF18 mRNA.

ABSTRACT: Fibroblast growth factor 18 (FGF18) emerges as a promising therapeutic target for osteoarthritis (OA). In this study, a novel articular cavity-localized lipid nanoparticle (LNP) named WG-PL14 is developed. This optimized formulation has a nearly 30-fold increase in mRNA expression as well as better articular cavity enrichment compared to commercial lipids MC3 when performing intra-articular injection. Then, a mRNA sequence encoding recombinant human FGF18 (rhFGF18) for potential mRNA therapy in OA is optimized. In vitro assays confirm the translation of rhFGF18 mRNA into functional proteins within rat and human chondrocytes, promoting cell proliferation and extracellular matrix (ECM) synthesis. Subsequently, the therapeutic efficacy of the LNP-rhFGF18 mRNA complex is systematically assesse

SUBMITTER: Sun M 

PROVIDER: S-EPMC11582510 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature