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bioRxiv · 10.1101/2024.01.11.575297

Optimization of Anticodon Edited Transfer RNAs (ACE-tRNAs) Function in Translation for Suppression of Nonsense Mutations

Porter, J. J.·Ko, W.·Sorensen, E. G.·Lueck, J. D.
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Abstract

Nonsense suppressor tRNAs or AntiCodon-Edited tRNAs (ACE-tRNAs) have long been envisioned as a therapeutic approach to overcome genetic diseases resulting from the introduction of premature stop codons (PTCs). The ACE-tRNA approach for the rescue of PTCs has been hampered by ineffective delivery through available modalities for gene therapy. Here we have screened a series of ACE-tRNA expression cassette sequence libraries containing >1,800 members to optimize ACE-tRNA function and provide a roadmap for optimization in the future. By optimizing PTC suppression efficiency of ACE-tRNAs, we have decreased the amount of ACE-tRNA required by [~]16-fold for the most common cystic fibrosis-causing PTCs.

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Porter, J. J., Ko, W., Sorensen, E. G., Lueck, J. D.. 2024-01-12. Optimization of Anticodon Edited Transfer RNAs (ACE-tRNAs) Function in Translation for Suppression of Nonsense Mutations. https://doi.org/10.1101/2024.01.11.575297

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