Engineered transfer RNAs for suppression of premature termination codons

DOI

Premature termination codons (PTCs) are responsible for 10-15% of all inherited disease. PTC suppression during translation offers a promising approach to treat a variety of genetic disorders, yet small molecules that promote PTC read-through have yielded mixed performance in clinical trials. We present a high-throughput, cell-based assay to identify anticodon engineered transfer RNAs (ACE-tRNA) which can effectively suppress in-frame PTCs and faithfully encode their cognate amino acid. In total, we identified ACE-tRNA with a high degree of suppression activity targeting the most common human disease-causing nonsense codons. Genome-wide transcriptome ribosome profiling of cells expressing ACE-tRNA at levels which repair PTC indicate that there are limited interactions with translation termination codons. These ACE-tRNAs display high suppression potency in mammalian cells, Xenopus oocytes and mice in vivo, producing PTC repair in multiple genes, including disease causing mutations within cystic fibrosis transmembrane conductance regulator (CFTR).

Identifier
DOI http://dx.doi.org/doi:10.17632/mgtfjbxxtf.1
Metadata Access https://easy.dans.knaw.nl/oai?verb=GetRecord&metadataPrefix=oai_datacite&identifier=oai:easy.dans.knaw.nl:easy-dataset:118253
Provenance
Creator YOON, J
Publisher Data Archiving and Networked Services (DANS)
Contributor Jae Seok YOON
Publication Year 2019
Rights info:eu-repo/semantics/openAccess;License: http://creativecommons.org/licenses/by/4.0
Contact Jae Seok YOON
Representation
Resource Type Dataset
Coverage
Discipline Various
Temporal Point 2019-02-18T11:59:59Z