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Fig 1. Natural tRNA recognizes a sense codon (e.g. UAC), whereas an engineered suppressor tRNA (sup-tRNA) recognizes a stop codon (UAG) with an amino acid. The rAAV delivered sup-tRNA rescued mucopolysaccharidosis type I disease having a nonsense mutation (W402X) in the IDUA gene.
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Our Customer’s Success Story
Nonsense mutations account for 11% of pathogenic mutations. Suppressor-tRNA engineered to read through the premature stop codon safely and efficiently rescued a genetic non-sense mutation disease delivered by rAAV gene therapy. The rAAV.sup-tRNA had limited global side effect at normal stop codons and did not perturb endogenous tRNA homeostasis, as determined by ribosome profiling and tRNA sequencing.
Suppressor-tRNAs therefore represent a valuable addition to full-length protein-coding gene replacement therapy.
References
Wang J. et al (2022) AAV-delivered suppressor tRNA overcomes a nonsense mutation in mice.
Nature 604(7905):343-348 [PMID:35322228]
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