{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:21:29Z","timestamp":1790360489884,"version":"4.1.0"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006351","name":"Colton Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006351","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35-GM118047"],"award-info":[{"award-number":["R35-GM118047"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>HK022 coliphage site-specific recombinase Integrase (Int) can catalyze integrative site-specific recombination and recombinase-mediated cassette exchange (RMCE) reactions in mammalian cell cultures. Owing to the promiscuity of the 7 bp overlap sequence in its att sites, active \u2018attB\u2019 sites flanking human deleterious mutations were previously identified that may serve as substrates for RMCE reactions for future potential gene therapy. However, the wild type Int proved inefficient in catalyzing such RMCE reactions. To address this low efficiency, variants of Int were constructed and examined by integrative site-specific recombination and RMCE assays in human cells using native \u2018attB\u2019 sites. As a proof of concept, various Int derivatives have demonstrated successful RMCE reactions using a pair of native \u2018attB\u2019 sites that were inserted as a substrate into the human genome. Moreover, successful RMCE reactions were demonstrated in native locations of the human CTNS and DMD genes whose mutations are responsible for Cystinosis and Duchene Muscular Dystrophy diseases, respectively. This work provides a steppingstone for potential downstream therapeutic applications.<\/jats:p>","DOI":"10.1093\/nar\/gkaa1140","type":"journal-article","created":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T12:07:07Z","timestamp":1604837227000},"page":"12804-12816","source":"Crossref","is-referenced-by-count":9,"title":["HK022 bacteriophage Integrase mediated RMCE as a potential tool for human gene therapy"],"prefix":"10.1093","volume":"48","author":[{"given":"Amer","family":"Elias","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Kassis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suha Abd","family":"Elkader","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Gritsenko","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Nahmad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hodaya","family":"Shir","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana","family":"Younis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atheer","family":"Shannan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7508-6230","authenticated-orcid":false,"given":"Hideki","family":"Aihara","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota TwinCities, Minneapolis, MN, 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gali","family":"Prag","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezra","family":"Yagil","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3473-2790","authenticated-orcid":false,"given":"Mikhail","family":"Kolot","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University,\u00a0Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"2020121502542753500_B1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.copbio.2014.06.005","article-title":"The genome editing toolbox: a spectrum of approaches for targeted modification","volume":"30C","author":"Cheng","year":"2014","journal-title":"Curr. 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