Chondrocyte-specific genomic editing enabled by hybrid exosomes for osteoarthritis treatment
Open accessAbstract
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.
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Two primary approaches can accomplish the loading of specific cargoes into exosomes: endogenous loading and exogenous loading.
“Two primary approaches can accomplish the loading of specific cargoes into exosomes.”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [94]
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- Authors
- Liang, Y., Xu, X., Xu, L., Iqbal, Z., Ouyang, K., Zhang, H., Wen, C., Duan, L., & Xia, J.
- Affiliations
- Chinese University of Hong Kong (HK)
- Shenzhen University (CN)
- Southern University of Science and Technology (CN)
- Hong Kong Polytechnic University (HK)
- Corresponding author
- Liang, Yujie
- Xu, Xiao
- Xu, Limei
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2022
- Volume
- 12
- Issue
- 11
- Pages
- 4866-4878
- ISSN
- 1838-7640 (ISSN-L)
- PMC
- PMC9274754
- OpenAlex
- W4285110131
- Cited by
- 217
- References
- 44
- Citations by year
- 2026: 49 · 2025: 60 · 2024: 60 · 2023: 44 · 2022: 4
- FWCI
- 30.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Theranostics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PolyU Institutional Research Archive (Hong Kong Polytechnic University) (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (2019/20, 81972116, 81972085, 81772394, 31900046)
- China Postdoctoral Science Foundation (81772394, 81972085, 81972116, 2020M682907)
- Chinese University of Hong Kong (RAC-2019/20)
- Basic and Applied Basic Research Foundation of Guangdong Province (2020A1515011581, 2021A1515010985)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- osteoarthritis, CRISPR/Cas9, Lamp2b, articular cartilage degeneration, extracellular matrix degradation, intra-articular administration
- MeSH terms
- Gene Editing, Animals, Cartilage, Articular, Liposomes, Osteoarthritis, Chondrocytes, Genomics, Rats, Matrix Metalloproteinase 13, Exosomes
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