{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T03:35:32Z","timestamp":1784345732190,"version":"3.55.0"},"reference-count":47,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&D Program of China","award":["2017YFE0103400"],"award-info":[{"award-number":["2017YFE0103400"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY028758"],"award-info":[{"award-number":["EY028758"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA013696"],"award-info":[{"award-number":["CA013696"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY030580"],"award-info":[{"award-number":["EY030580"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OD020351"],"award-info":[{"award-number":["OD020351"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY027285"],"award-info":[{"award-number":["EY027285"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY019007"],"award-info":[{"award-number":["EY019007"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY018213"],"award-info":[{"award-number":["EY018213"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY024698"],"award-info":[{"award-number":["EY024698"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY026682"],"award-info":[{"award-number":["EY026682"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG050437"],"award-info":[{"award-number":["AG050437"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001116","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","award":["PPA-1218-0751-COLU"],"award-info":[{"award-number":["PPA-1218-0751-COLU"]}],"id":[{"id":"10.13039\/100001116","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Schneeweiss Stem Cell Fund","award":["SDHDOH01-C32590GG-3450000"],"award-info":[{"award-number":["SDHDOH01-C32590GG-3450000"]}]},{"name":"Nancy & Kobi Karp"},{"name":"Crowley Family Funds"},{"name":"Rosenbaum Family Foundation"},{"DOI":"10.13039\/100007817","name":"Alcon Research Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007817","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Gebroe Family Foundation"},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Physician-Scientist Award"],"award-info":[{"award-number":["Physician-Scientist Award"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM127652"],"award-info":[{"award-number":["GM127652"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY028758"],"award-info":[{"award-number":["EY028758"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Irma T. Hirschl\/Monique Weill-Caulier Trust","award":["Research Award"],"award-info":[{"award-number":["Research Award"]}]},{"DOI":"10.13039\/100006474","name":"Columbia University","doi-asserted-by":"publisher","award":["Faculty Recruitment Award"],"award-info":[{"award-number":["Faculty Recruitment Award"]}],"id":[{"id":"10.13039\/100006474","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Genetic mutation of the human\n                    <jats:italic>BEST1<\/jats:italic>\n                    gene, which encodes a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated Cl\n                    <jats:sup>-<\/jats:sup>\n                    channel (BEST1) predominantly expressed in retinal pigment epithelium (RPE), causes a spectrum of retinal degenerative disorders commonly known as bestrophinopathies. Previously, we showed that BEST1 plays an indispensable role in generating Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent Cl\n                    <jats:sup>-<\/jats:sup>\n                    currents in human RPE cells, and the deficiency of BEST1 function in patient-derived RPE is rescuable by gene augmentation (Li et al., 2017). Here, we report that\n                    <jats:italic>BEST1<\/jats:italic>\n                    patient-derived loss-of-function and gain-of-function mutations require different mutant to wild-type (WT) molecule ratios for phenotypic manifestation, underlying their distinct epigenetic requirements in bestrophinopathy development, and suggesting that some of the previously classified autosomal dominant mutations actually behave in a dominant-negative manner. Importantly, the strong dominant effect of\n                    <jats:italic>BEST1<\/jats:italic>\n                    gain-of-function mutations prohibits the restoration of BEST1-dependent Cl\n                    <jats:sup>-<\/jats:sup>\n                    currents in RPE cells by gene augmentation, in contrast to the efficient rescue of loss-of-function mutations via the same approach. Moreover, we demonstrate that gain-of-function mutations are rescuable by a combination of gene augmentation with CRISPR\/Cas9-mediated knockdown of endogenous\n                    <jats:italic>BEST1<\/jats:italic>\n                    expression, providing a universal treatment strategy for all bestrophinopathy patients regardless of their mutation types.\n                  <\/jats:p>","DOI":"10.7554\/elife.67622","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T13:48:17Z","timestamp":1622555297000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.67622","source":"Crossref","is-referenced-by-count":23,"title":["Distinct expression requirements and rescue strategies for BEST1 loss- and gain-of-function mutations"],"prefix":"10.7554","volume":"10","author":[{"given":"Qingqing","family":"Zhao","sequence":"first","affiliation":[{"name":"Eye Center, Renmin Hospital of Wuhan University, Wuhan, China"},{"name":"Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, Rochester, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Vagelos College of Physicians & Surgeons, Columbia University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8140-9267","authenticated-orcid":true,"given":"Alec","family":"Kittredge","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Columbia University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Vagelos College of Physicians & Surgeons, Columbia University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4201-3948","authenticated-orcid":true,"given":"Yin","family":"Shen","sequence":"additional","affiliation":[{"name":"Eye Center, Medical Research Institute, Renmin Hospital, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Vagelos College of Physicians & Surgeons, Columbia University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H","family":"Tsang","sequence":"additional","affiliation":[{"name":"Jonas Children\u2019s Vision Care, Departments of Ophthalmology and Pathology & Cell Biology, Edward S. Harkness Eye Institute, Institute of Human Nutrition and Columbia Stem Cell Initiative, New York Presbyterian Hospital\/Columbia University Irving Medical Center, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5220-588X","authenticated-orcid":true,"given":"Tingting","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, Rochester, United States"},{"name":"Department of Ophthalmology, Vagelos College of Physicians & Surgeons, Columbia University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s004390050986","article-title":"Evaluation of the best disease gene in patients with age-related macular degeneration and other maculopathies","volume":"104","author":"Allikmets","year":"1999","journal-title":"Human Genetics"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ajo.2016.05.024","article-title":"Unilateral BEST1-Associated retinopathy","volume":"169","author":"Arora","year":"2016","journal-title":"American Journal of Ophthalmology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1016\/j.ccell.2018.10.003","article-title":"Widespread selection for oncogenic mutant allele imbalance in Cancer","volume":"34","author":"Bielski","year":"2018","journal-title":"Cancer Cell"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1146\/annurev-cancerbio-051320-124252","article-title":"Mutant allele imbalance in Cancer","volume":"5","author":"Bielski","year":"2021","journal-title":"Annual Review of Cancer Biology"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.ajhg.2007.08.004","article-title":"Biallelic mutation of BEST1 causes a distinct retinopathy in humans","volume":"82","author":"Burgess","year":"2008","journal-title":"The American Journal of Human Genetics"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1038\/eye.2010.180","article-title":"Best's macular dystrophy in Australia: phenotypic profile and identification of novel BEST1 mutations","volume":"25","author":"Cohn","year":"2011","journal-title":"Eye"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.ajhg.2009.09.015","article-title":"Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa","volume":"85","author":"Davidson","year":"2009","journal-title":"The American Journal of Human Genetics"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1097\/IAE.0000000000000387","article-title":"New best1 mutations in autosomal recessive bestrophinopathy","volume":"35","author":"Fung","year":"2015","journal-title":"Retina"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"2574","DOI":"10.1038\/nprot.2014.173","article-title":"Screening and large-scale expression of membrane proteins in mammalian cells for structural studies","volume":"9","author":"Goehring","year":"2014","journal-title":"Nature Protocols"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.stem.2014.05.018","article-title":"An iCRISPR platform for rapid, multiplexable, and inducible genome editing in human pluripotent stem cells","volume":"15","author":"Gonz\u00e1lez","year":"2014","journal-title":"Cell Stem Cell"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1152\/physrev.00022.2007","article-title":"Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies","volume":"88","author":"Hartzell","year":"2008","journal-title":"Physiological Reviews"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.stem.2009.07.002","article-title":"Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells","volume":"5","author":"Idelson","year":"2009","journal-title":"Cell Stem Cell"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/s42003-019-0433-3","article-title":"Dual Ca2+-dependent Gates in human Bestrophin1 underlie disease-causing mechanisms of gain-of-function mutations","volume":"2","author":"Ji","year":"2019","journal-title":"Communications Biology"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-54892-7","article-title":"Investigation and restoration of BEST1 activity in Patient-derived RPEs with dominant mutations","volume":"9","author":"Ji","year":"2019","journal-title":"Scientific Reports"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.exer.2014.02.006","article-title":"Disease-causing mutations associated with four bestrophinopathies exhibit disparate effects on the localization, but not the Oligomerization, of Bestrophin-1","volume":"121","author":"Johnson","year":"2014","journal-title":"Experimental Eye Research"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.preteyeres.2017.01.006","article-title":"Bestrophin 1 and retinal disease","volume":"58","author":"Johnson","year":"2017","journal-title":"Progress in Retinal and Eye Research"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nature13913","article-title":"Structure and insights into the function of a ca(2+)-activated cl(-) channel","volume":"516","author":"Kane Dickson","year":"2014","journal-title":"Nature"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.exer.2016.12.003","article-title":"Anoctamin2 (TMEM16B) forms the Ca2+-activated Cl- channel in the retinal pigment epithelium","volume":"154","author":"Keckeis","year":"2017","journal-title":"Experimental Eye Research"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.3791\/57791","article-title":"Differentiation, maintenance, and analysis of human retinal pigment epithelium cells: a Disease-in-a-dish model for BEST1\u00a0mutations","volume":"138","author":"Kittredge","year":"2018","journal-title":"Journal of Visualized Experiments"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/sj.ejhg.5200447","article-title":"Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration","volume":"8","author":"Kr\u00e4mer","year":"2000","journal-title":"European Journal of Human Genetics"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/7651_2015_225","article-title":"Skin biopsy and Patient-Specific stem cell lines","volume":"1353","author":"Li","year":"2016","journal-title":"Methods in Molecular Biology"},{"key":"bib22","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29914","article-title":"Patient-specific mutations impair bestrophin1's essential role in mediating Ca2+-dependent Cl- currents in human RPE","volume":"6","author":"Li","year":"2017","journal-title":"eLife"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.3390\/genes8100283","article-title":"Allelic expression imbalance in the human retinal transcriptome and potential impact on inherited retinal diseases","volume":"8","author":"Llavona","year":"2017","journal-title":"Genes"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1101\/gr.1006603","article-title":"Allelic variation in gene expression is common in the human genome","volume":"13","author":"Lo","year":"2003","journal-title":"Genome Research"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"3612","DOI":"10.1167\/iovs.05-1622","article-title":"Confluent monolayers of cultured human fetal retinal pigment epithelium exhibit morphology and physiology of native tissue","volume":"47","author":"Maminishkis","year":"2006","journal-title":"Investigative Opthalmology & Visual Science"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"12758","DOI":"10.1073\/pnas.220402097","article-title":"Bestrophin, the product of the best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium","volume":"97","author":"Marmorstein","year":"2000","journal-title":"PNAS"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1093\/hmg\/7.9.1517","article-title":"Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best's disease)","volume":"7","author":"Marquardt","year":"1998","journal-title":"Human Molecular Genetics"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.1093\/hmg\/ddw126","article-title":"Bestrophin1 mutations cause defective chloride conductance in patient stem cell-derived RPE","volume":"25","author":"Moshfegh","year":"2016","journal-title":"Human Molecular Genetics"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/s41594-020-0402-z","article-title":"Structural and functional characterization of the bestrophin-2 anion channel","volume":"27","author":"Owji","year":"2020","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/915","article-title":"Identification of the gene responsible for best macular dystrophy","volume":"19","author":"Petrukhin","year":"1998","journal-title":"Nature Genetics"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1534\/genetics.115.176263","article-title":"Allelic imbalance is a prevalent and Tissue-Specific feature of the mouse transcriptome","volume":"200","author":"Pinter","year":"2015","journal-title":"Genetics"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01966-z","article-title":"Allelic imbalance of somatic mutations in Cancer genomes and transcriptomes","volume":"7","author":"Rhee","year":"2017","journal-title":"Scientific Reports"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1007\/s00424-016-1898-2","article-title":"Expression of anoctamins in retinal pigment epithelium (RPE)","volume":"468","author":"Schreiber","year":"2016","journal-title":"Pfl\u00fcgers Archiv - European Journal of Physiology"},{"key":"bib34","first-page":"2736","article-title":"BEST1 sequence variants in italian patients with vitelliform macular dystrophy","volume":"18","author":"Sodi","year":"2012","journal-title":"Molecular Vision"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"4008","DOI":"10.1073\/pnas.052692999","article-title":"The vitelliform macular dystrophy protein defines a new family of chloride channels","volume":"99","author":"Sun","year":"2002","journal-title":"PNAS"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1016\/j.ophtha.2018.04.001","article-title":"CRISPR-based genome surgery for the treatment of autosomal dominant retinitis pigmentosa","volume":"125","author":"Tsai","year":"2018","journal-title":"Ophthalmology"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/ng799","article-title":"Small changes in expression affect predisposition to tumorigenesis","volume":"30","author":"Yan","year":"2002","journal-title":"Nature Genetics"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072545","article-title":"Allelic variation in human gene expression","volume":"297","author":"Yan","year":"2002","journal-title":"Science"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1038\/nchembio.2007.42","article-title":"Genetically encoded molecules for inducibly inactivating CaV channels","volume":"3","author":"Yang","year":"2007","journal-title":"Nature Chemical Biology"},{"key":"bib40","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3540","article-title":"Bio-inspired voltage-dependent calcium channel blockers","volume":"4","author":"Yang","year":"2013","journal-title":"Nature Communications"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1126\/science.1259723","article-title":"Structure and selectivity in bestrophin ion channels","volume":"346","author":"Yang","year":"2014","journal-title":"Science"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"18213","DOI":"10.1073\/pnas.1420984111","article-title":"Preassociated apocalmodulin mediates Ca2+-dependent sensitization of activation and inactivation of TMEM16A\/16B Ca2+-gated cl- channels","volume":"111","author":"Yang","year":"2014","journal-title":"PNAS"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1038\/mt.2015.177","article-title":"BEST1: the best target for gene and cell therapies","volume":"23","author":"Yang","year":"2015","journal-title":"Molecular Therapy"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"3683","DOI":"10.1167\/iovs.04-0550","article-title":"Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC)","volume":"45","author":"Yardley","year":"2004","journal-title":"Investigative Opthalmology & Visual Science"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/s41592-018-0048-5","article-title":"An enhanced CRISPR repressor for targeted mammalian gene regulation","volume":"15","author":"Yeo","year":"2018","journal-title":"Nature Methods"},{"key":"bib46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05616-4","article-title":"ATP activates bestrophin ion channels through direct interaction","volume":"9","author":"Zhang","year":"2018","journal-title":"Nature Communications"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/B978-0-12-801185-0.00011-8","article-title":"The iCRISPR platform for rapid genome editing in human pluripotent stem cells","volume":"546","author":"Zhu","year":"2014","journal-title":"Methods in Enzymology"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/67622\/elife-67622-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/67622\/elife-67622-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/67622","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:13:37Z","timestamp":1697058817000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/67622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,1]]},"references-count":47,"alternative-id":["10.7554\/eLife.67622"],"URL":"https:\/\/doi.org\/10.7554\/elife.67622","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.67622.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.67622.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,1]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e67622"}}