Cellular and tissue selectivity of aav serotypes for gene delivery to chondrocytes and cartilage

Dong Suk Yoon, Kyoung Mi Lee, Sehee Cho, Eun Ae Ko, Jihyun Kim, Sujin Jung, Jae Hyuck Shim, Guangping Gao, Kwang Hwan Park, Jin Woo Lee

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3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3353-3360
Number of pages8
JournalInternational Journal of Medical Sciences
Issue number15
Publication statusPublished - 2021

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2019R1I1A1A01060928 and NRF-202 0R1I1A1A01054892). JHS holds support from NIAMS of the NIH under R01AR068983 and the AAVAA Therapeutics. GG holds support from grants under the NIH (P01AI100263, R01NS076991, P01HD080642, R01AI12135). This research was also conducted through a grant funded by AAVAA Therapeutics Inc (South Korea).

Publisher Copyright:
© The author(s).

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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