Department of Medicine, Division of Rheumatology; Li Weibo Institute for Rare Diseases Research; Horae Gene Therapy Center; Department of Microbiology and Physiological Systems; Viral Vector Core
Cell Biology | Genetics and Genomics | Musculoskeletal Diseases | Therapeutics
Background: Despite several studies on the effect of adeno-associated virus (AAV)-based therapeutics on osteoarthritis (OA), information on the transduction efficiency and applicable profiles of different AAV serotypes to chondrocytes in hard cartilage tissue is still limited. Moreover, the recent discovery of additional AAV serotypes makes it necessary to screen for more suitable AAV serotypes for specific tissues. Here, we compared the transduction efficiencies of 14 conventional AAV serotypes in human chondrocytes, mouse OA models, and human cartilage explants obtained from OA patients.
Methods: To compare the transduction efficiency of individual AAV serotypes, green fluorescent protein (GFP) expression was detected by fluorescence microscopy or western blotting. Likewise, to compare the transduction efficiencies of individual AAV serotypes in cartilage tissues, GFP expression was determined using fluorescence microscopy or immunohistochemistry, and GFP-positive cells were counted.
Results: Only AAV2, 5, 6, and 6.2 exhibited substantial transduction efficiencies in both normal and OA chondrocytes. All AAV serotypes except AAV6 and rh43 could effectively transduce human bone marrow mesenchymal stem cells. In human and mouse OA cartilage tissues, AAV2, AAV5, AAV6.2, AAV8, and AAV rh39 showed excellent tissue specificity based on transduction efficiency. These results indicate the differences in transduction efficiencies of AAV serotypes between cellular and tissue models.
Conclusions: Our findings indicate that AAV2 and AAV6.2 may be the best choices for AAV-mediated gene delivery into intra-articular cartilage tissue. These AAV vectors hold the potential to be of use in clinical applications to prevent OA progression if appropriate therapeutic genes are inserted into the vector.
Adeno-associated virus (AAV) serotypes, Chondrocytes, Gene therapy, Osteoarthritis
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DOI of Published Version
Yoon DS, Lee KM, Cho S, Ko EA, Kim J, Jung S, Shim JH, Gao G, Park KH, Lee JW. Cellular and Tissue Selectivity of AAV Serotypes for Gene Delivery to Chondrocytes and Cartilage. Int J Med Sci. 2021 Jul 25;18(15):3353-3360. doi: 10.7150/ijms.56760. PMID: 34522160; PMCID: PMC8436087. Link to article on publisher's site
International journal of medical sciences
Yoon DS, Lee K, Cho S, Ko EA, Kim J, Jung S, Shim J, Gao G, Park KH, Lee JW. (2021). Cellular and Tissue Selectivity of AAV Serotypes for Gene Delivery to Chondrocytes and Cartilage. Open Access Publications by UMass Chan Authors. https://doi.org/10.7150/ijms.56760. Retrieved from https://escholarship.umassmed.edu/oapubs/4842
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This work is licensed under a Creative Commons Attribution 4.0 License.