Hydroxyapatite Binding Peptide Lipid Nanoparticles for Biomimetic mRNA Delivery to Bone

• DOI: 10.1002/adtp.202400505
• Publication Date: 2025-04-17T14:15:15Z
• Authors: Joshua A. Choe; Jena E. Moseman; Jamie M. Jones; Jacobus C. Burger; Ashley M. Weichmann; Douglas G. McNeel; William L. Murphy

AbstractDevelopment of strategies for non‐viral gene delivery targeted to bone can be used for bone pathologies. Applications include rheumatologic disease, metastatic disease to the bone, pathologies with deficits in hematopoiesis, osteomyelitis, and regenerative medicine. However, specific delivery to tissues like bone is challenging. Here mRNA LNPs (lipid nanoparticles) decorated with a biomimetic hydroxyapatite‐binding peptide (HABP‐LNP) are described, which show improved binding to bone minerals compared to sham peptide conjugated mRNA LNPs (Sham‐LNP). The HABP‐LNPs also increase transfection when associated with bone mineral. Furthermore, HABP mRNA LNPs improve intraosseous transfection and reduce hepatic uptake in vivo. The continued development of these mRNA LNPs can result in non‐viral therapies for bone pathologies.