{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326462/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326462"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Nonviral delivery of chemically modified tRNA rescues nonsense mutations","description":"Suppressor transfer RNAs (sup-tRNAs) can rescue disease-causing nonsense mutations by promoting readthrough of premature termination codons (PTCs). Their clinical translation is limited by suboptimal activity and inefficient in vivo delivery. In this work, we combined site-specific chemical modification of sup-tRNAs with cargo-tailored pulmonary lipid nanoparticle (LNP) engineering to overcome these barriers. Incorporation of N1-methyladenosine in sup-tRNAs improved PTC readthrough, enhanced tRNA aminoacylation, prolonged functional persistence, and reduced innate immune activation. High-throughput ionizable lipid screening and formulation optimization identified a sup-tRNA–tailored LNP that efficiently delivered chemically modified sup-tRNAs to the lung. This approach restored cystic fibrosis transmembrane conductance regulator (CFTR) expression and function in bronchial epithelial cells, mouse models, and patient-derived organoids. Thus, LNP-delivered, chemically engineered sup-tRNAs represent a potential therapeutic platform for treating nonsense mutations.","dates":{"publication":"2026/08/27"},"accession":"GSE326462","cross_references":{"GSM":["GSM9632114","GSM9632113","GSM9632112","GSM9632111","GSM9632110","GSM9632099","GSM9632098","GSM9632097","GSM9632119","GSM9632118","GSM9632117","GSM9632116","GSM9632115","GSM9632103","GSM9632102","GSM9632101","GSM9632123","GSM9632100","GSM9632122","GSM9632121","GSM9632120","GSM9632109","GSM9632108","GSM9632107","GSM9632106","GSM9632105","GSM9632104"],"GPL":["34281"],"GSE":["326462"],"taxon":["Homo sapiens"],"PMID":["[42658930]"]}}