Int J Med Sci 2021; 18(15):3353-3360. doi:10.7150/ijms.56760 This issue

Research Paper

Cellular and Tissue Selectivity of AAV Serotypes for Gene Delivery to Chondrocytes and Cartilage

Dong Suk Yoon1#, Kyoung-Mi Lee1,2#, Sehee Cho1,3#, Eun Ae Ko1, Jihyun Kim1, Sujin Jung1, Jae-Hyuck Shim4,5,6, Guangping Gao5,6,7,8, Kwang Hwan Park1✉, Jin Woo Lee1,2,3✉

1. Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul 03722, South Korea
2. Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, South Korea
3. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea
4. Division of Rheumatology, University of Massachusetts Medical School, Worcester, MA 01605, USA
5. Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, MA 01605, USA
6. Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA
7. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA
8. Viral Vector Core, University of Massachusetts Medical School, Worcester, MA 01605, USA
# DSY, K-ML, and SC contributed equally to this work and are co-first authors to this article.

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Citation:
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; 18(15):3353-3360. doi:10.7150/ijms.56760. Available from https://www.medsci.org/v18p3353.htm

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Abstract

Graphic abstract

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.

Keywords: Adeno-associated virus (AAV) serotypes, Chondrocytes, Osteoarthritis, Gene therapy