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Chondrocyte-specific genomic editing enabled by hybrid exosomes for osteoarthritis treatment
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Chondrocyte-specific genomic editing enabled by hybrid exosomes for osteoarthritis treatment
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Journal Article
Chondrocyte-specific genomic editing enabled by hybrid exosomes for osteoarthritis treatment
2022
Overview
A cell-specific delivery vehicle is required to achieve gene editing of the disease-associated cells, so the hereditable genome editing reactions are confined within these cells without affecting healthy cells. A hybrid exosome-based nano-sized delivery vehicle derived by fusion of engineered exosomes and liposomes will be able to encapsulate and deliver CRISPR/Cas9 plasmids selectively to chondrocytes embedded in articular cartilage and attenuate the condition of cartilage damage.
Chondrocyte-targeting exosomes (CAP-Exo) were constructed by genetically fusing a chondrocyte affinity peptide (CAP) at the N-terminus of the exosomal surface protein Lamp2b. Membrane fusion of the CAP-Exo with liposomes formed hybrid CAP-exosomes (hybrid CAP-Exo) which were used to encapsulate CRISPR/Cas9 plasmids. By intra-articular (IA) administration, hybrid CAP-Exo/Cas9 sgMMP-13 entered the chondrocytes of rats with cartilage damages that mimicked the condition of osteoarthritis.
The hybrid CAP-Exo entered the deep region of the cartilage matrix in arthritic rats on IA administration, delivered the plasmid Cas9 sgMMP-13 to chondrocytes, knocked down the matrix metalloproteinase 13 (
), efficiently ablated the expression of
in chondrocytes, and attenuated the hydrolytic degradation of the extracellular matrix proteins in the cartilage.
Chondrocyte-specific knockdown of
mitigates or prevents cartilage degradation in arthritic rats, showing that hybrid CAP-Exo/Cas9 sgMMP-13 may alleviate osteoarthritis.
Publisher
Ivyspring International Publisher Pty Ltd,Ivyspring International Publisher
