{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:52:30Z","timestamp":1790747550122,"version":"4.1.0"},"reference-count":32,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T00:00:00Z","timestamp":1457913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T00:00:00Z","timestamp":1457913600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T00:00:00Z","timestamp":1457913600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["311682"],"award-info":[{"award-number":["311682"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["TMESMT211TT"],"award-info":[{"award-number":["TMESMT211TT"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Transcription factors (TFs) operate by the combined activity of their DNA-binding domains (DBDs) and effector domains (EDs) enabling the coordination of gene expression on a genomic scale. Here we show that in vivo delivery of an engineered DNA-binding protein uncoupled from the repressor domain can produce efficient and gene-specific transcriptional silencing. To interfere with RHODOPSIN (\n                    <jats:italic>RHO<\/jats:italic>\n                    ) gain-of-function mutations we engineered the ZF6-DNA-binding protein (ZF6-DB) that targets 20 base pairs (bp) of a\n                    <jats:italic>RHOcis<\/jats:italic>\n                    -regulatory element (CRE) and demonstrate\n                    <jats:italic>Rho<\/jats:italic>\n                    specific transcriptional silencing upon adeno-associated viral (AAV) vector-mediated expression in photoreceptors. The data show that the 20 bp-long genomic DNA sequence is necessary for\n                    <jats:italic>RHO<\/jats:italic>\n                    expression and that photoreceptor delivery of the corresponding cognate synthetic trans-acting factor ZF6-DB without the intrinsic transcriptional repression properties of the canonical ED blocks\n                    <jats:italic>Rho<\/jats:italic>\n                    expression with negligible genome-wide transcript perturbations. The data support DNA-binding-mediated silencing as a novel mode to treat gain-of-function mutations.\n                  <\/jats:p>","DOI":"10.7554\/elife.12242","type":"journal-article","created":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T08:59:42Z","timestamp":1457945982000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.12242","source":"Crossref","is-referenced-by-count":40,"title":["Rhodopsin targeted transcriptional silencing by DNA-binding"],"prefix":"10.7554","volume":"5","author":[{"given":"Salvatore","family":"Botta","sequence":"first","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Marrocco","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"de Prisco","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Curion","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Renda","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Sofia","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Lupo","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Carissimo","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Bacci","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Gesualdo","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Settimio","family":"Rossi","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Simonelli","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2975-942X","authenticated-orcid":true,"given":"Enrico Maria","family":"Surace","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Napoli, Italy"},{"name":"Department of Translational Medicine, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2016,3,14]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1089\/104303401450988","article-title":"Isolation of highly infectious and pure adeno-associated virus type 2 vectors with a single-step gravity-flow column","volume":"12","author":"Auricchio","year":"2001","journal-title":"Human Gene 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