AAV-delivered UGA suppressor tRNA for disease-agnostic in vivo gene therapy

1. Wang, J. et al. AAV-delivered suppressor tRNA overcomes a nonsense mutation in mice. Nature 604, 343–348 (2021). This paper reports that UAG-sup-tRNA delivered by rAAV rescues the disease-associated PTC in multiple tissues in a mouse model of Hurler syndrome.

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2. Albers, S. et al. Engineered tRNAs suppress nonsense mutations in cells and in vivo. Nature 618, 842–848 (2023). This paper reports that an in vitro transcribed UGA-sup-tRNA delivered via LNPs in mice mediates efficient readthrough of the PTC in a co-delivered reporter mRNA.

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3. Pierce, S. E. et al. Prime editing-installed suppressor tRNAs for disease-agnostic genome editing. Nature https://doi.org/10.1038/s41586-025-09732-2 (2025). This paper uses prime editing to convert an endogenous tRNA into a UAG-sup-tRNA and rescues disease pathology in a mouse model of Hurler syndrome.

4. Mullick, A. et al. The cumate gene-switch: a system for regulated expression in mammalian cells. BMC Biotechnol. 6, 43 (2006). This paper uses the bacterial operator–repressor CymR/CuO system to control gene expression in mammalian cells.

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5. Porter, J. J. et al. Optimization of ACE-tRNAs function in translation for suppression of nonsense mutations. Nucleic Acids Res. 52, 14112–14132 (2024). This paper optimizes the flanking and body sequences of sup-tRNA to improve PTC suppression efficiency in vitro.

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This is a summary of: Xu, M. et al. An engineered UGA suppressor tRNA gene for disease-agnostic AAV delivery. Nat. Biotechnol. https://doi.org/10.1038/s41587-025-02982-5 (2026).