{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:32:15Z","timestamp":1773275535071,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T00:00:00Z","timestamp":1558396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T00:00:00Z","timestamp":1558396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A cytosine to thymine mutation at nucleotide 654 of human \u03b2-globin intron 2 (\u03b2<jats:sup>IVS2-654<\/jats:sup>) is one of the most common mutations causing \u03b2-thalassaemia in Chinese and Southeast Asians. This mutation results in aberrant \u03b2-globin pre-mRNA splicing and prevents synthesis of \u03b2-globin protein. Splicing correction using synthetic splice-switching oligonucleotides (SSOs) has been shown to restore expression of the \u03b2-globin protein, but to maintain therapeutically relevant levels of \u03b2-globin it would require lifelong administration. Here, we demonstrate long-term splicing correction using U7 snRNA lentiviral vectors engineered to target several pre-mRNA splicing elements on the \u03b2<jats:sup>IVS2-654<\/jats:sup>-globin pre-mRNA such as cryptic 3\u2032 splice site, aberrant 5\u2032 splice site, cryptic branch point and an exonic splicing enhancer. A double-target engineered U7 snRNAs targeted to the cryptic branch point and an exonic splicing enhancer, U7.BP\u2009+\u2009623, was the most effective in a model cell line, HeLa IVS2-654. Moreover, the therapeutic potential of the vector was demonstrated in erythroid progenitor cells derived from \u03b2<jats:sup>IVS2-654<\/jats:sup>-thalassaemia\/HbE patients, which showed restoration of correctly spliced \u03b2-globin mRNA and led to haemoglobin A synthesis, and consequently improved thalassaemic erythroid cell pathology. These results demonstrate proof of concept of using the engineered U7 snRNA lentiviral vector for treatment of \u03b2-thalassaemia.<\/jats:p>","DOI":"10.1038\/s41598-019-43964-3","type":"journal-article","created":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T10:11:42Z","timestamp":1558433502000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Restoration of correct \u03b2IVS2-654-globin mRNA splicing and HbA production by engineered U7 snRNA in \u03b2-thalassaemia\/HbE erythroid cells"],"prefix":"10.1038","volume":"9","author":[{"given":"Tiwaporn","family":"Nualkaew","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natee","family":"Jearawiriyapaisarn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suradej","family":"Hongeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suthat","family":"Fucharoen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryszard","family":"Kole","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-9838","authenticated-orcid":false,"given":"Saovaros","family":"Svasti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,5,21]]},"reference":[{"key":"43964_CR1","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/S0140-6736(11)60283-3","volume":"379","author":"DR Higgs","year":"2012","unstructured":"Higgs, D. 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