Bone-targeting engineered exosomes delivering teriparatide mRNA for the treatment of osteoporosis

Introduction

Teriparatide (TPTD) is an established osteoanabolic agent for the treatment of osteoporosis; however, its short circulating half-life necessitates repeated administration, while limited skeletal selectivity may reduce delivery efficiency. To address these limitations, we developed an Asp6-functionalized, bone-targeting exosome system carrying TPTD mRNA (Asp6-Exo@TPTD). An Exo-Motif sequence was incorporated into the TPTD mRNA construct to facilitate hnRNPA2B1-associated enrichment of the transcript in exosomes, while surface modification with the hydroxyapatite-binding peptide Asp6 was used to enhance skeletal affinity. BMSC-derived exosomes may additionally provide intrinsic regenerative signals that complement the osteoanabolic activity of TPTD.