Delivery of FGF18 using mRNA-LNP protects the cartilage against degeneration via alleviating chondrocyte senescence.

ABSTRACT:

Background

Osteoarthritis (OA) is a degenerative joint disease with an immense unmet medical need. FGF18 protein is a potential regenerative factor for cartilage repair. However, traditional protein delivery methods have limited efficacy due to the short lifetime and shallow infiltration.

Results

In this work, we discovered that lipid nanoparticle (LNP) can infiltrate and deliver FGF18 mRNA deeper in the cartilage than proteins. After mRNA UTR optimization and chemical modification, the expression of FGF18 can last up to 6 days in the cartilage. Furthermore, delivering FGF18 mRNA activates FOXO3a-autophagy pathway, which protects against chondrocyte degeneration and senescence. Local intra-articular injection of FGF18 mRNA-LNP significantly alleviates OA symptoms in DMM and

SUBMITTER: Kong K 

PROVIDER: S-EPMC11753171 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature