Wang, D., Tai, P. W. L. & Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 18, 358–378 (2019).
Google Scholar
Li, C. & Samulski, R. J. Engineering adeno-associated virus vectors for gene therapy. Nat. Rev. Genet. 21, 255–272 (2020).
Google Scholar
Mendell, J. R. et al. Current clinical applications of in vivo gene therapy with AAVs. Mol. Ther. 29, 464–488 (2020).
Google Scholar
Hordeaux, J. et al. Adeno-associated virus-induced dorsal root ganglion pathology. Hum. Gene Ther. 31, 808–818 (2020).
Google Scholar
Van Alstyne, M. et al. Gain of toxic function by long-term AAV9-mediated SMN overexpression in the sensorimotor circuit. Nat. Neurosci. 24, 930–940 (2021).
Google Scholar
Golebiowski, D. et al. Direct intracranial injection of AAVrh8 encoding monkey β-N-acetylhexosaminidase causes neurotoxicity in the primate brain. Hum. Gene Ther. 28, 510–522 (2017).
Google Scholar
Wang, D., Zhang, F. & Gao, G. CRISPR-based therapeutic genome editing: strategies and in vivo delivery by AAV vectors. Cell 181, 136–150 (2020).
Google Scholar
Chang, J. C., Temple, G. F., Trecartin, R. F. & Kan, Y. W. Suppression of the nonsense mutation in homozygous β0 thalassaemia. Nature 281, 602–603 (1979).
Google Scholar
Temple, G. F., Dozy, A. M., Roy, K. L. & Kan, Y. W. Construction of a functional human suppressor tRNA gene: an approach to gene therapy for β-thalassaemia. Nature 296, 537–540 (1982).
Google Scholar
Porter, J. J., Heil, C. S. & Lueck, J. D. Therapeutic promise of engineered nonsense suppressor tRNAs. Wiley Interdiscip. Rev. RNA. 12, e1641 (2021).
Google Scholar
Wang, D. et al. Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA–W402X mutation. Mol. Genet. Metab. 99, 62–71 (2010).
Google Scholar
Bigger, B. W., Begley, D. J., Virgintino, D. & Pshezhetsky, A. V. Anatomical changes and pathophysiology of the brain in mucopolysaccharidosis disorders. Mol. Genet. Metab. 125, 322–331 (2018).
Google Scholar
Hampe, C. S. et al. Mucopolysaccharidosis type I: current treatments, limitations, and prospects for improvement. Biomolecules 11, 189 (2021).
Google Scholar
Ingolia, N. T., Ghaemmaghami, S., Newman, J. R. & Weissman, J. S. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324, 218–223 (2009).
Google Scholar
Wangen, J. R. & Green, R. Stop codon context influences genome-wide stimulation of termination codon readthrough by aminoglycosides. eLife. 9, e52611 (2020).
Google Scholar
Behrens, A., Rodschinka, G. & Nedialkova, D. D. High-resolution quantitative profiling of tRNA abundance and modification status in eukaryotes by mim-tRNAseq. Mol. Cell 81, 1802–1815.e7 (2021).
Google Scholar
Koukuntla, R., Ramsey, W. J., Young, W. B. & Link, C. J. U6 promoter-enhanced GlnUAG suppressor tRNA has higher suppression efficacy and can be stably expressed in 293 cells. J. Gene Med. 15, 93–101 (2013).
Google Scholar
Keeling, K. M., Xue, X., Gunn, G. & Bedwell, D. M. Therapeutics based on stop codon readthrough. Annu. Rev. Genomics Hum. Genet. 15, 371–394 (2014).
Google Scholar
Manuvakhova, M., Keeling, K. & Bedwell, D. M. Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system. RNA 6, 1044–1055 (2000).
Google Scholar
Phillips-Jones, M. K., Hill, L. S., Atkinson, J. & Martin, R. Context effects on misreading and suppression at UAG codons in human cells. Mol. Cell. Biol. 15, 6593–6600 (1995).
Google Scholar
Roy, B. et al. Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression. Proc. Natl Acad. Sci. USA 113, 12508–12513 (2016).
Google Scholar
Xue, X. et al. Identification of the amino acids inserted during suppression of CFTR nonsense mutations and determination of their functional consequences. Hum. Mol. Genet. 26, 3116–3129 (2017).
Google Scholar
Lueck, J. D. et al. Engineered transfer RNAs for suppression of premature termination codons. Nat. Commun. 10, 822 (2019).
Google Scholar
Giege, R., Sissler, M. & Florentz, C. Universal rules and idiosyncratic features in tRNA identity. Nucleic Acids Res. 26, 5017–5035 (1998).
Google Scholar
Bunge, S. et al. Genotype–phenotype correlations in mucopolysaccharidosis type I using enzyme kinetics, immunoquantification and in vitro turnover studies. Biochim. Biophys. Acta 1407, 249–256 (1998).
Google Scholar
Oussoren, E. et al. Residual α-l-iduronidase activity in fibroblasts of mild to severe mucopolysaccharidosis type I patients. Mol. Genet. Metab. 109, 377–381 (2013).
Google Scholar
Parker, D. J. et al. Growth-optimized aminoacyl-tRNA synthetase levels prevent maximal tRNA charging. Cell Syst. 11, 121–130.e6 (2020).
Google Scholar
Hinnebusch, A. G. Translational regulation of GCN4 and the general amino acid control of yeast. Annu. Rev. Microbiol. 59, 407–450 (2005).
Google Scholar
Buvoli, M., Buvoli, A. & Leinwand, L. A. Suppression of nonsense mutations in cell culture and mice by multimerized suppressor tRNA genes. Mol. Cell. Biol. 20, 3116–3124 (2000).
Google Scholar
Xie, J. et al. Short DNA hairpins compromise recombinant adeno-associated virus genome homogeneity. Mol. Ther. 25, 1363–1374 (2017).
Google Scholar
Davidoff, A. M., Ng, C. Y., Zhou, J., Spence, Y. & Nathwani, A. C. Sex significantly influences transduction of murine liver by recombinant adeno-associated viral vectors through an androgen-dependent pathway. Blood 102, 480–488 (2003).
Google Scholar
Keeling, K. M. et al. Leaky termination at premature stop codons antagonizes nonsense-mediated mRNA decay in S. cerevisiae. RNA 10, 691–703 (2004).
Google Scholar
Kim, Y. K., Furic, L., Desgroseillers, L. & Maquat, L. E. Mammalian Staufen1 recruits Upf1 to specific mRNA 3′UTRs so as to elicit mRNA decay. Cell 120, 195–208 (2005).
Google Scholar
Maquat, L. E., Tarn, W. Y. & Isken, O. The pioneer round of translation: features and functions. Cell 142, 368–374 (2010).
Google Scholar
van Tol, H. & Beier, H. All human tRNATyr genes contain introns as a prerequisite for pseudouridine biosynthesis in the anticodon. Nucleic Acids Res. 16, 1951–1966 (1988).
Google Scholar
Dong, J., Qiu, H., Garcia-Barrio, M., Anderson, J. & Hinnebusch, A. G. Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-binding domain. Mol. Cell 6, 269–279 (2000).
Google Scholar
Fechter, P., Rudinger-Thirion, J., Theobald-Dietrich, A. & Giege, R. Identity of tRNA for yeast tyrosyl-tRNA synthetase: tyrosylation is more sensitive to identity nucleotides than to structural features. Biochemistry 39, 1725–1733 (2000).
Google Scholar
Kurosaki, T., Popp, M. W. & Maquat, L. E. Quality and quantity control of gene expression by nonsense-mediated mRNA decay. Nat. Rev. Mol. Cell Biol. 20, 406–420 (2019).
Google Scholar
Colombo, M., Karousis, E. D., Bourquin, J., Bruggmann, R. & Muhlemann, O. Transcriptome-wide identification of NMD-targeted human mRNAs reveals extensive redundancy between SMG6- and SMG7-mediated degradation pathways. RNA 23, 189–201 (2017).
Google Scholar
Huang, L. et al. Targeting translation termination machinery with antisense oligonucleotides for diseases caused by nonsense mutations. Nucleic Acid Ther. 29, 175–186 (2019).
Google Scholar
Wang, J. et al. In vivo delivery of suppressor tRNA overcomes a pathogenic nonsense mutation in mice. Mol. Ther. 29, S128 (2021).
Chan, K. Y. et al. Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nat. Neurosci. 20, 1172–1179 (2017).
Google Scholar
Moreno, A. M. et al. Immune-orthogonal orthologues of AAV capsids and of Cas9 circumvent the immune response to the administration of gene therapy. Nat. Biomed. Eng. 3, 806–816 (2019).
Google Scholar
Li, A. et al. AAV-CRISPR gene editing is negated by pre-existing immunity to Cas9. Mol. Ther. 28, 1432–1441 (2020).
Google Scholar
Gadalla, K. K. et al. Improved survival and reduced phenotypic severity following AAV9/MECP2 gene transfer to neonatal and juvenile male Mecp2 knockout mice. Mol. Ther. 21, 18–30 (2013).
Google Scholar
Kramarski, L. & Arbely, E. Translational read-through promotes aggregation and shapes stop codon identity. Nucleic Acids Res. 48, 3747–3760 (2020).
Google Scholar
Hashimoto, S., Nobuta, R., Izawa, T. & Inada, T. Translation arrest as a protein quality control system for aberrant translation of the 3′-UTR in mammalian cells. FEBS Lett. 593, 777–787 (2019).
Google Scholar
Arribere, J. A. et al. Translation readthrough mitigation. Nature 534, 719–723 (2016).
Google Scholar
Lombardi, S. et al. Translational readthrough of GLA nonsense mutations suggests dominant-negative effects exerted by the interaction of wild-type and missense variants. RNA Biol. 17, 254–263 (2020).
Google Scholar
Kuzmin, D. A. et al. The clinical landscape for AAV gene therapies. Nat. Rev. Drug Discov. 20, 173–174 (2021).
Google Scholar
Keller, A., Nesvizhskii, A. I., Kolker, E. & Aebersold, R. Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal. Chem. 74, 5383–5392 (2002).
Google Scholar
Nesvizhskii, A. I., Keller, A., Kolker, E. & Aebersold, R. A statistical model for identifying proteins by tandem mass spectrometry. Anal. Chem. 75, 4646–4658 (2003).
Google Scholar
Ingolia, N. T., Brar, G. A., Rouskin, S., McGeachy, A. M. & Weissman, J. S. The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. Nat. Protoc. 7, 1534–1550 (2012).
Google Scholar
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Google Scholar
Yukselen, O., Turkyilmaz, O., Ozturk, A. R., Garber, M. & Kucukural, A. DolphinNext: a distributed data processing platform for high throughput genomics. BMC Genomics 21, 310 (2020).
Google Scholar
Clarke, L. A. et al. Murine mucopolysaccharidosis type I: targeted disruption of the murine α-l-iduronidase gene. Hum. Mol. Genet. 6, 503–511 (1997).
Google Scholar
Wang, D. et al. The designer aminoglycoside NB84 significantly reduces glycosaminoglycan accumulation associated with MPS I-H in the Idua–W392X mouse. Mol. Genet. Metab. 105, 116–125 (2012).
Google Scholar
Wang, D. et al. Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice. Nat. Biotechnol. 36, 839–842 (2018).
Google Scholar
Crowe, A. R. & Yue, W. Semi-quantitative determination of protein expression using immunohistochemistry staining and analysis: an integrated protocol. Bio Protoc. 9, e3465 (2019).
Google Scholar
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
Google Scholar
Evans, M. E., Clark, W. C., Zheng, G. & Pan, T. Determination of tRNA aminoacylation levels by high-throughput sequencing. Nucleic Acids Res. 45, e133 (2017).
Google Scholar

