FAP-Synergistic Organ-Targeted mRNA-LNP for Overcoming Delivery Barriers in Hepatic and Pulmonary Fibrosis - PubMed
4 hours ago
- #lipid nanoparticles
- #fibrosis therapy
- #mRNA delivery
- Developed FOCUS (Fibrosis Organ and Cell Unified-Targeting System) for mRNA delivery using LNPs (lipid nanoparticles).
- Combines ionizable lipid library with FAP-targeting ligands for enhanced mRNA delivery to fibrotic tissues.
- Achieves 3-fold and 12-fold greater mRNA expression in fibrotic liver and lung, respectively.
- Demonstrates 2-5-fold higher fibroblast distribution compared to organ- or ligand-only targeting.
- Proof of concept: mPTX-2-loaded FOCUS LNPs reduce collagen deposition by 60-80% in murine models.
- Avoids systemic side effects like impaired wound healing.
- Mechanism: Suppresses monocyte-to-fibrocyte differentiation, M2 macrophage polarization, and fibroblast activation.
- Establishes a precision mRNA delivery platform for safer and more effective fibrotic disease therapy.