{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:10:00Z","timestamp":1793405400313,"version":"4.5.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T00:00:00Z","timestamp":1540425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0206158","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T20:49:57Z","timestamp":1540500597000},"page":"e0206158","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":37,"title":["The minor gentamicin complex component, X2, is a potent premature stop codon readthrough molecule with therapeutic potential"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-2973","authenticated-orcid":true,"given":"Westley J.","family":"Friesen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jairo","family":"Sierra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Vazirani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiao","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Tomizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramil","family":"Baiazitov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie","family":"Morrill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Babu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Choon","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Art","family":"Branstrom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mollin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Hedrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Sheedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Elfring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marla","family":"Weetall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Colacino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M.","family":"Welch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart W.","family":"Peltz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,10,25]]},"reference":[{"issue":"8","key":"ref1","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/humu.20763","article-title":"A meta-analysis of nonsense mutations causing human genetic disease","volume":"29","author":"M Mort","year":"2008","journal-title":"Hum Mutat"},{"issue":"6","key":"ref2","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1073\/pnas.0711795105","article-title":"PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model","volume":"105","author":"M Du","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ref3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1172\/JCI70462","article-title":"Postnatal manipulation of Pax6 dosage reverses congenital tissue malformation defects","volume":"124","author":"CY Gregory-Evans","year":"2014","journal-title":"J Clin Invest"},{"issue":"1","key":"ref4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/hmg\/ddu428","article-title":"The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy","volume":"24","author":"JN Miller","year":"2015","journal-title":"Hum Mol Genet"},{"issue":"16","key":"ref5","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1093\/hmg\/ddw184","article-title":"Functional rescue of REP1 following treatment with PTC124 and novel derivative PTC-414 in human choroideremia fibroblasts and the nonsense-mediated zebrafish model","volume":"25","author":"M Moosajee","year":"2016","journal-title":"Hum Mol Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev-med-120611-144851","article-title":"Ataluren as an agent for therapeutic nonsense suppression","volume":"64","author":"SW Peltz","year":"2013","journal-title":"Annu Rev Med"},{"issue":"7140","key":"ref7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nature05756","article-title":"PTC124 targets genetic disorders caused by nonsense mutations","volume":"447","author":"EM Welch","year":"2007","journal-title":"Nature"},{"issue":"4","key":"ref8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/mus.24332","article-title":"Ataluren treatment of patients with nonsense mutation dystrophinopathy","volume":"50","author":"K Bushby","year":"2014","journal-title":"Muscle Nerve"},{"issue":"12","key":"ref9","doi-asserted-by":"crossref","first-page":"e81302","DOI":"10.1371\/journal.pone.0081302","article-title":"Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy","volume":"8","author":"RS Finkel","year":"2013","journal-title":"PLoS One"},{"issue":"10101","key":"ref10","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0140-6736(17)31611-2","article-title":"Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","volume":"390","author":"CM Mcdonald","year":"2017","journal-title":"Lancet"},{"issue":"1","key":"ref11","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.nmd.2014.11.011","article-title":"European Medicines Agency review of ataluren for the treatment of ambulant patients aged 5 years and older with Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene","volume":"25","author":"M Haas","year":"2015","journal-title":"Neuromuscul Disord"},{"issue":"4","key":"ref12","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1261\/rna.060236.116","article-title":"The nucleoside analog clitocine is a potent and efficacious readthrough agent","volume":"23","author":"WJ Friesen","year":"2017","journal-title":"RNA"},{"issue":"4","key":"ref13","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nm0496-467","article-title":"Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations","volume":"2","author":"M Howard","year":"1996","journal-title":"Nat Med"},{"issue":"51","key":"ref14","doi-asserted-by":"crossref","first-page":"E10899","DOI":"10.1073\/pnas.1715501114","article-title":"Aminoglycoside interactions and impacts on the eukaryotic ribosome","volume":"114","author":"I Prokhorova","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ref15","doi-asserted-by":"crossref","DOI":"10.1183\/23120541.00080-2017","article-title":"Factors influencing readthrough therapy for frequent cystic fibrosis premature termination codons","volume":"4","author":"I Pranke","year":"2018","journal-title":"ERJ Open Res"},{"issue":"6","key":"ref16","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1177\/0897190014546836","article-title":"Aminoglycoside-induced nephrotoxicity","volume":"27","author":"KA Wargo","year":"2014","journal-title":"J Pharm Pract"},{"issue":"2\u20133","key":"ref17","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.tox.2008.04.015","article-title":"Aminoglycoside induced ototoxicity","volume":"249","author":"OW Guthrie","year":"2008","journal-title":"Toxicology"},{"issue":"7","key":"ref18","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1164\/ajrccm.163.7.2004001","article-title":"Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis","volume":"163","author":"JP Clancy","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"issue":"11","key":"ref19","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.tig.2008.08.010","article-title":"Introducing sense into nonsense in treatments of human genetic diseases","volume":"24","author":"L Linde","year":"2008","journal-title":"Trends Genet"},{"issue":"6","key":"ref20","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1177\/1756285610388693","article-title":"Aminoglycoside-induced mutation suppression (stop codon readthrough) as a therapeutic strategy for Duchenne muscular dystrophy","volume":"3","author":"V Malik","year":"2010","journal-title":"Ther Adv Neurol Disord"},{"issue":"1","key":"ref21","first-page":"15","article-title":"Gentamicin administration in Duchenne patients with premature stop codon. Preliminary results","volume":"22","author":"L Politano","year":"2003","journal-title":"Acta Myol"},{"issue":"1","key":"ref22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1183\/09031936.00120910","article-title":"Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis","volume":"38","author":"M Wilschanski","year":"2011","journal-title":"Eur Respir J"},{"issue":"3","key":"ref23","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1080\/15476286.2017.1285480","article-title":"Characterization of new-generation aminoglycoside promoting premature termination codon readthrough in cancer cells","volume":"14","author":"L Bidou","year":"2017","journal-title":"RNA Biol"},{"issue":"17","key":"ref24","doi-asserted-by":"crossref","first-page":"6265","DOI":"10.1093\/nar\/13.17.6265","article-title":"Suppression of a nonsense mutation in mammalian cells in vivo by the aminoglycoside antibiotics G-418 and paromomycin","volume":"13","author":"JF Burke","year":"1985","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"ref25","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1042\/BA20080266","article-title":"Development of K562 cell clones expressing beta-globin mRNA carrying the beta039 thalassaemia mutation for the screening of correctors of stop-codon mutations","volume":"54","author":"F Salvatori","year":"2009","journal-title":"Biotechnol Appl Biochem"},{"issue":"8","key":"ref26","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/mrc.1222","article-title":"Assignment of the major and minor components of gentamicin for evaluation of batches","volume":"41","author":"R Deubner","year":"2003","journal-title":"Magnetic Resonance in Chemistry"},{"issue":"11\u201312","key":"ref27","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1365\/s10337-010-1763-y","article-title":"Determination of Gentamicin Sulphate Composition and Related Substances in Pharmaceutical Preparations by LC with Charged Aerosol Detection","volume":"72","author":"K Stypulkowska","year":"2010","journal-title":"Chromatographia"},{"issue":"8","key":"ref28","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1023\/A:1027372416983","article-title":"Component composition of gentamicin sulfate preparations","volume":"37","author":"AF Vydrin","year":"2003","journal-title":"Pharmaceutical Chemistry Journal (Translation of Khimiko-Farmatsevticheskii Zhurnal)"},{"issue":"3","key":"ref29","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/hmg\/10.3.291","article-title":"Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of alpha-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation","volume":"10","author":"KM Keeling","year":"2001","journal-title":"Hum Mol Genet"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/S0165-4608(99)00253-8","article-title":"Establishment and characterization of a new cell line derived from a human primary breast carcinoma","volume":"120","author":"CS Wang","year":"2000","journal-title":"Cancer Genet Cytogenet"},{"issue":"44","key":"ref31","doi-asserted-by":"crossref","first-page":"12508","DOI":"10.1073\/pnas.1605336113","article-title":"Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression","volume":"113","author":"B Roy","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref32","article-title":"Exploratory Data Analysis","author":"J Tukey","year":"1977","journal-title":"Exploratory Data Analysis"},{"issue":"3","key":"ref33","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/00031305.1978.10479267","article-title":"On Fieller&apos;s Theorem and the General Linear Model","volume":"32","author":"G Zerbe","year":"1978","journal-title":"The American Statistician"},{"issue":"4","key":"ref34","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S0887-2333(99)00060-0","article-title":"Overview of the Final MEIC Results","volume":"13","author":"C Clemedson","year":"1999","journal-title":"I. The In Vitro\u2014In Vitro Evaluation. Toxicology in Vitro"},{"issue":"2","key":"ref35","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s10162-008-0118-y","article-title":"Using the zebrafish lateral line to screen for ototoxicity","volume":"9","author":"LL Chiu","year":"2008","journal-title":"J Assoc Res Otolaryngol"},{"issue":"7519","key":"ref36","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature13737","article-title":"Structural basis for the inhibition of the eukaryotic ribosome","volume":"513","author":"LN Garreau de","year":"2014","journal-title":"Nature"},{"issue":"1\u20132","key":"ref37","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.heares.2005.05.005","article-title":"The use of zebrafish for assessing ototoxic and otoprotective agents","volume":"208","author":"C Ton","year":"2005","journal-title":"Hear Res"},{"issue":"1\u20132","key":"ref38","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0378-5955(00)00039-3","article-title":"Cell turnover in neuromasts of zebrafish larvae","volume":"143","author":"JA Williams","year":"2000","journal-title":"Hear Res"},{"issue":"1","key":"ref39","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1128\/AAC.23.1.74","article-title":"Aminoglycoside accumulation kinetics in rat renal parenchyma","volume":"23","author":"GR Aronoff","year":"1983","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"ref40","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2133\/dmpk.19.159","article-title":"Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity","volume":"19","author":"J Nagai","year":"2004","journal-title":"Drug Metab Pharmacokinet"},{"issue":"13","key":"ref41","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1073\/pnas.1620982114","article-title":"Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity","volume":"114","author":"A Baradaran-Heravi","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"ref42","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1039\/C4MD00081A","article-title":"When Proteins Start to Make Sense: Fine-tuning Aminoglycosides for PTC Suppression Therapy","volume":"5","author":"M Shalev","year":"2014","journal-title":"Medchemcomm"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0008-6215(93)84244-Z","article-title":"Microscopic protonation constants in tobramycin. An NMR and pH study with the aid of partially N-acetylated derivatives","volume":"247","author":"L Szilagyi","year":"1993","journal-title":"Carbohydr Res"},{"issue":"23","key":"ref44","doi-asserted-by":"crossref","first-page":"10630","DOI":"10.1021\/jm3012992","article-title":"Increased selectivity toward cytoplasmic versus mitochondrial ribosome confers improved efficiency of synthetic aminoglycosides in fixing damaged genes: a strategy for treatment of genetic diseases caused by nonsense mutations","volume":"55","author":"J Kandasamy","year":"2012","journal-title":"J Med Chem"},{"issue":"2","key":"ref45","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1039\/B712690P","article-title":"Designer aminoglycosides: the race to develop improved antibiotics and compounds for the treatment of human genetic diseases","volume":"6","author":"M Hainrichson","year":"2008","journal-title":"Org Biomol Chem"},{"issue":"8","key":"ref46","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1039\/C4MD00081A","article-title":"When Proteins Start to Make Sense: Fine-tuning Aminoglycosides for PTC Suppression Therapy","volume":"5","author":"M Shalev","year":"2014","journal-title":"Medchemcomm"},{"issue":"4","key":"ref47","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1074\/jbc.M113.533588","article-title":"Designer aminoglycosides that selectively inhibit cytoplasmic rather than mitochondrial ribosomes show decreased ototoxicity: a strategy for the treatment of genetic diseases","volume":"289","author":"E Shulman","year":"2014","journal-title":"J Biol Chem"},{"issue":"4","key":"ref48","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1165\/rcmb.2013-0282OC","article-title":"Synthetic aminoglycosides efficiently suppress cystic fibrosis transmembrane conductance regulator nonsense mutations and are enhanced by ivacaftor","volume":"50","author":"X Xue","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"2","key":"ref49","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1681\/ASN.2011040325","article-title":"Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury","volume":"23","author":"AM Ralib","year":"2012","journal-title":"J Am Soc Nephrol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0206158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T19:35:59Z","timestamp":1720726559000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0206158"}},"subtitle":[],"editor":[{"given":"Georg","family":"Stoecklin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,10,25]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0206158","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,25]]}}}