Anticodon-engineered tRNAs restore full-length MeCP2 expression and function in Rett syndrome nonsense mutations

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Rett syndrome is primarily caused by loss-of-function mutations in the MECP2 gene, with nonsense mutations being a significant contributor.
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ACE-tRNAs effectively promote readthrough of MECP2 nonsense mutations, restoring full-length and functional MeCP2 protein.
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Readthrough efficiency varies among different nonsense mutations, indicating the need for mutation-specific optimization of ACE-tRNAs.
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ACE-tRNA-rescued MeCP2 demonstrates correct localization and functional interactions, essential for its activity in the cell.
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ACE-tRNA-based readthrough strategies represent a promising approach for treating RTT-associated nonsense mutations.

Frontiers In Neurology

by Elena Fara, Stefano Pezzini, Ginevra Arpaia, Angelisa Frasca, Joseph J. Porter, John D. Lueck, Nicoletta Landsberger
June 1, 2026

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