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dc.contributor.authorYoon, Dong Suk
dc.contributor.authorLee, Kyoung-Mi
dc.contributor.authorCho, Sehee
dc.contributor.authorKo, Eun Ae
dc.contributor.authorKim, Jihyun
dc.contributor.authorJung, Sujin
dc.contributor.authorShim, Jae-Hyuck
dc.contributor.authorGao, Guangping
dc.contributor.authorPark, Kwang Hwan
dc.contributor.authorLee, Jin Woo
dc.date2022-08-11T08:10:01.000
dc.date.accessioned2022-08-23T16:52:22Z
dc.date.available2022-08-23T16:52:22Z
dc.date.issued2021-07-25
dc.date.submitted2022-01-18
dc.identifier.citation<p>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. <a href="https://doi.org/10.7150/ijms.56760">Link to article on publisher's site</a></p>
dc.identifier.issn1449-1907 (Linking)
dc.identifier.doi10.7150/ijms.56760
dc.identifier.pmid34522160
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42038
dc.description.abstractBackground: 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=34522160&dopt=Abstract">Link to Article in PubMed</a></p>
dc.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.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAdeno-associated virus (AAV) serotypes
dc.subjectChondrocytes
dc.subjectGene therapy
dc.subjectOsteoarthritis
dc.subjectCell Biology
dc.subjectGenetics and Genomics
dc.subjectMusculoskeletal Diseases
dc.subjectTherapeutics
dc.titleCellular and Tissue Selectivity of AAV Serotypes for Gene Delivery to Chondrocytes and Cartilage
dc.typeJournal Article
dc.source.journaltitleInternational journal of medical sciences
dc.source.volume18
dc.source.issue15
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5875&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4842
dc.identifier.contextkey27504115
refterms.dateFOA2022-08-23T16:52:22Z
html.description.abstract<p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p>
dc.identifier.submissionpathoapubs/4842
dc.contributor.departmentViral Vector Core
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.contributor.departmentHorae Gene Therapy Center
dc.contributor.departmentLi Weibo Institute for Rare Diseases Research
dc.contributor.departmentDepartment of Medicine, Division of Rheumatology
dc.source.pages3353-3360


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© 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.
Except where otherwise noted, this item's license is described as © 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.