{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:17:34Z","timestamp":1792804654360,"version":"4.5.0"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre from Poland","award":["Etiuda 2016\/20\/T\/NZ4\/00525"],"award-info":[{"award-number":["Etiuda 2016\/20\/T\/NZ4\/00525"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Science Centre from Poland","award":["Preludium 2016\/23\/N\/NZ4\/03228"],"award-info":[{"award-number":["Preludium 2016\/23\/N\/NZ4\/03228"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"crossref"}]},{"name":"BEAT-PCD project (EU COST Action 1407)","award":["Short Term Scientific Mission (STSM)"],"award-info":[{"award-number":["Short Term Scientific Mission (STSM)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary ciliary dyskinesia (PCD) is a rare disease with autosomal recessive inheritance, caused mostly by bi-allelic gene mutations that impair motile cilia structure and function. Currently, there are no causal treatments for PCD. In many disease models, translational readthrough of premature termination codons (PTC-readthrough) induced by aminoglycosides has been proposed as an effective way of restoring functional protein expression and reducing disease symptoms. However, variable outcomes of pre-clinical trials and toxicity associated with long-term use of aminoglycosides prompt the search for other compounds that might overcome these problems. Because a high proportion of PCD-causing variants are nonsense mutations, readthrough therapies are an attractive option. We tested a group of chemical compounds with known PTC-readthrough potential (ataluren, azithromycin, tylosin, amlexanox, and the experimental compound TC007), collectively referred to as non-aminoglycosides (NAGs). We investigated their PTC-readthrough efficiency in six PTC mutations found in Polish PCD patients, in the context of cell and cilia health, and in comparison to the previously tested aminoglycosides. The NAGs did not compromise the viability of the primary nasal respiratory epithelial cells, and the ciliary beat frequency was retained, similar to what was observed for gentamicin. In HEK293 cells transfected with six PTC-containing inserts, the tested compounds stimulated PTC-readthrough but with lower efficiency than aminoglycosides. The study allowed us to select compounds with minimal negative impact on cell viability and function but still the potential to induce PTC-readthrough.<\/jats:p>","DOI":"10.3390\/ijms22094923","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T10:06:12Z","timestamp":1620381972000},"page":"4923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Properties of Non-Aminoglycoside Compounds Used to Stimulate Translational Readthrough of PTC Mutations in Primary Ciliary Dyskinesia"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4150-3985","authenticated-orcid":false,"given":"Maciej","family":"Dabrowski","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6945-1059","authenticated-orcid":false,"given":"Zuzanna","family":"Bukowy-Bieryllo","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1200-0935","authenticated-orcid":false,"given":"Claire L.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Primary Ciliary Dyskinesia Centre, NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"},{"name":"School of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Zietkiewicz","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/path.4843","article-title":"Motile and non-motile cilia in human pathology: From function to phenotypes","volume":"241","author":"Mitchison","year":"2017","journal-title":"J. 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