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http://hdl.handle.net/10397/94146
Title: | Chondrocyte-specific genomic editing enabled by hybrid exosomes for osteoarthritis treatment | Authors: | Liang, Y Xu, X Xu, L Iqbal, Z Ouyang, K Zhang, H Wen, C Duan, L Xia, J |
Issue Date: | 2022 | Source: | Theranostics, 2022, v. 12, no. 11, p. 4866-4878 | Abstract: | Rationale: 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. Methods: 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. Results: 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 (MMP-13), efficiently ablated the expression of MMP-13 in chondrocytes, and attenuated the hydrolytic degradation of the extracellular matrix proteins in the cartilage. Conclusion: Chondrocyte-specific knockdown of MMP-13 mitigates or prevents cartilage degradation in arthritic rats, showing that hybrid CAP-Exo/Cas9 sgMMP-13 may alleviate osteoarthritis. |
Keywords: | Cartilage CRISPR/Cas9 Hybrid exosome MMP-13 Osteoarthritis Therapeutic genome editing |
Publisher: | Ivyspring International Publisher | Journal: | Theranostics | EISSN: | 1838-7640 | DOI: | 10.7150/thno.69368 | Rights: | © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. The following publication Liang Y, Xu X, Xu L, Iqbal Z, Ouyang K, Zhang H, Wen C, Duan L, Xia J. Chondrocyte-specific genomic editing enabled by hybrid exosomes for osteoarthritis treatment. Theranostics 2022; 12(11):4866-4878 is available at https://dx.doi.org/10.7150/thno.69368. |
Appears in Collections: | Journal/Magazine Article |
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