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Chondrocyte-Targeted MicroRNA Delivery by Engineered Exosomes toward a Cell-Free Osteoarthritis Therapy
journal contribution
posted on 2020-08-07, 08:29 authored by Yujie Liang, Xiao Xu, Xingfu Li, Jianyi Xiong, Biquan Li, Li Duan, Daping Wang, Jiang XiaTargeted
delivery
to the diseased cell
or tissue is the key to the successful clinical use of nucleic acid
drugs. In particular, delivery of microRNA-140 (miRNA-140, miR-140)
into chondrocytes across the dense, nonvascular extracellular matrix
of cartilage remains a major challenge. Here, we report the chondrocyte-targeting
exosomes as vehicles for the delivery of miR-140 into chondrocytes
as a new treatment for osteoarthritis (OA). By fusing a chondrocyte-affinity
peptide (CAP) with the lysosome-associated membrane glycoprotein 2b
protein on the surface of exosomes, we acquire CAP-exosomes that can
efficiently encapsulate miR-140, specifically enter, and deliver the
cargo into chondrocytes in vitro. CAP-exosomes, in contrast to nontagged
exosome vesicles, are retained in the joints after intra-articular
injection with minimal diffusion in vivo. CAP-exosomes also deliver
miR-140 to deep cartilage regions through the dense mesochondrium,
inhibit cartilage-degrading proteases, and alleviate OA progression
in a rat model, pointing toward a potential organelle-based, cell-free
therapy of OA.