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Given that the expression of SARS-CoV-2 structural proteins is hampered by suboptimal codon usage in mammalian cells, the coding sequences for the SARS-CoV-2 S, M, N, and E proteins were firstly codon-optimized for mammalian cells (Supplementary Table 1). Western blot analysis showed that the protein expression of all four optimized genes was significantly higher than that of the corresponding wild type in HEK293T cells (Supplementary Fig. 1).

Introduction AAV is one of the most promising viral vectors for gene therapy due to its excellent safety, long-term expression, and high infectivity to a broad range of cell types (McCarty et al., 2004; Li et al., 2011; Gaj et al., 2016). Nearly 250 rAAV-mediated therapies have been used in clinical trials, and six approved for commercial use (Bryant et al., 2013; Smalley, 2017; Dangouloff and Servais, 2019; Kirschner et al., 2020; Keam, 2022; Ozelo et al., 2022; Heo, 2023).

Zhaoyue Zheng1, Jingya Ye1, Mi Leng1, Chunmei Gan1, Na tang2, Wei Li3, C. A. Valencia1, Biao Dong1, 2* and Hoi Y. Chow1* 1National Clinical Research Center for Geriatrics and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China 2Sichuan Real & Best Biotech Co., Ltd, China 3Department of Dermatovenereology, Rare Disease Center, West China Hospital, Sichuan University, China The final, formatted version of the article will be published soon.