{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:56:29Z","timestamp":1787331389812,"version":"build-2736575974"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0182974","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T21:30:02Z","timestamp":1502487002000},"page":"e0182974","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":48,"title":["Highly efficient gene inactivation by adenoviral CRISPR\/Cas9 in human primary cells"],"prefix":"10.1371","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-9211","authenticated-orcid":true,"given":"Olaf","family":"Voets","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans","family":"Tielen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edo","family":"Elstak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Benschop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Grimbergen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Stallen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"van Marle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Essrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,8,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/S1359-6446(05)03590-7","article-title":"Biology calls the targets: combining RNAi and disease biology","volume":"10","author":"H van Es","year":"2005","journal-title":"Drug Discov Today"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature02371","article-title":"A large-scale RNAi screen in human cells identifies new components of the p53 pathway","volume":"428","author":"K Berns","year":"2004","journal-title":"Nature"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nbt831","article-title":"Expression profiling reveals off-target gene regulation by RNAi","volume":"21","author":"AL Jackson","year":"2003","journal-title":"Nat Biotechnol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1128\/MCB.01524-13","article-title":"Transcription factor GATA1 is dispensable for mast cell differentiation in adult mice","volume":"34","author":"K Ohneda","year":"2014","journal-title":"Mol Cell Biol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.tibtech.2013.04.004","article-title":"ZFN, TALEN, and CRISPR\/Cas-based methods for genome engineering","volume":"31","author":"T Gaj","year":"2013","journal-title":"Trends Biotechnol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nbt.2842","article-title":"CRISPR-Cas systems for editing, regulating and targeting genomes","volume":"32","author":"JD Sander","year":"2014","journal-title":"Nat Biotechnol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1126\/science.1138140","article-title":"CRISPR provides acquired resistance against viruses in prokaryotes","volume":"315","author":"R Barrangou","year":"2007","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity","volume":"337","author":"M Jinek","year":"2012","journal-title":"Science"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1099\/mic.0.023960-0","article-title":"Short motif sequences determine the targets of the prokaryotic CRISPR defence system","volume":"155","author":"FJM Mojica","year":"2009","journal-title":"Microbiology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.1247005","article-title":"Genome-scale CRISPR-Cas9 knockout screening in human cells","volume":"343","author":"O Shalem","year":"2014","journal-title":"Science"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1126\/science.1246981","article-title":"Genetic screens in human cells using the CRISPR-Cas9 system","volume":"343","author":"T Wang","year":"2014","journal-title":"Science"},{"key":"ref12","article-title":"Adenoviral vector DNA for accurate genome editing with engineered nucleases","author":"M Holkers","year":"2014","journal-title":"Nat Methods"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"9592","DOI":"10.1038\/srep09592","article-title":"CRISPR\/Cas9-mediated endogenous protein tagging for RESOLFT super-resolution microscopy of living human cells","volume":"5","author":"M Ratz","year":"2015","journal-title":"Sci Rep"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.stem.2013.11.002","article-title":"Functional repair of CFTR by CRISPR\/Cas9 in intestinal stem cell organoids of cystic fibrosis patients","volume":"13","author":"G Schwank","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"gku749","DOI":"10.1093\/nar\/gku749","article-title":"Multiplex CRISPR\/Cas9-based genome engineering from a single lentiviral vector","volume":"42","author":"a. M Kabadi","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"ref16","article-title":"Inhibition of HIV-1 infection of primary CD4+ T cells by gene editing of CCR5 using adenovirus-delivered CRISPR\/Cas9","author":"C Li","year":"2015","journal-title":"J Gen Virol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1161\/CIRCRESAHA.117.306290","article-title":"Efficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR\/Cas9","volume":"117","author":"P Abrahimi","year":"2015","journal-title":"Circ Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"150819140043007","DOI":"10.1056\/NEJMoa1502214","article-title":"FTO Obesity Variant Circuitry and Adipocyte Browning in Humans","volume":"373","author":"M Claussnitzer","year":"2015","journal-title":"N Engl J Med"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"447","DOI":"10.2174\/1566523215666150812115939","article-title":"CFTR Inactivation by Lentiviral Vector-mediated RNA Interference and CRISPR-Cas9 Genome Editing in Human Airway Epithelial Cells","volume":"15","author":"J Bellec","year":"2015","journal-title":"Curr Gene Ther"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"L51","DOI":"10.1152\/ajplung.2000.278.1.L51","article-title":"Regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins","volume":"278","author":"S Van Wetering","year":"2000","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1101\/gr.1332603","article-title":"Adenoviral vectors expressing siRNAs for discovery and validation of gene function","volume":"13","author":"GJ Arts","year":"2003","journal-title":"Genome Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1038\/nbt746","article-title":"Arrayed adenoviral expression libraries for functional screening","volume":"20","author":"F Michiels","year":"2002","journal-title":"Nat Biotechnol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1194\/jlr.M700571-JLR200","article-title":"Improved lipid profile through liver-specific knockdown of liver X receptor alpha in KKAy diabetic mice","volume":"50","author":"JF Rippmann","year":"2009","journal-title":"J Lipid Res"},{"key":"ref24","article-title":"Multiplex Genome Engineering Using CRISPR \/ Cas Systems","volume":"819","author":"L Cong","year":"2013","journal-title":"Science"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/nrm2262","article-title":"Extracellular control of TGFbeta signalling in vascular development and disease","volume":"8","author":"P Ten Dijke","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.cell.2016.05.053","article-title":"Leveraging rules of nonsense-mediated mRNA decay for genome engineering and personalized medicine","author":"MW Popp","year":"2016","journal-title":"Cell"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"4093","DOI":"10.2174\/138161212802430396","article-title":"Cellular Players in Lung Fibrosis","author":"A N. Lekkerkerker","year":"2012","journal-title":"Current Pharmaceutical Design"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1165\/rcmb.2003-0063OC","article-title":"Smad3 mediates transforming growth factor-beta-induced alpha-smooth muscle actin expression","volume":"29","author":"B Hu","year":"2003","journal-title":"Am J Respir Cell Mol Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1038\/sj.onc.1203693","article-title":"Smad-dependent stimulation of type I collagen gene expression in human skin fibroblasts by TGF-beta involves functional cooperation with p300\/CBP transcriptional coactivators","volume":"19","author":"K Ghosh a","year":"2000","journal-title":"Oncogene"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"E2579","DOI":"10.1073\/pnas.1208507109","article-title":"PNAS Plus: Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria","volume":"109","author":"G Gasiunas","year":"2012","journal-title":"Proc Natl Acad Sci"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.molcel.2015.02.032","article-title":"Expanding the Biologist\u2019s Toolkit with CRISPR-Cas9","volume":"58","author":"SH Sternberg","year":"2015","journal-title":"Mol Cell"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nmeth.2532","article-title":"Heritable genome editing in C. elegans via a CRISPR-Cas9 system","volume":"10","author":"AE Friedland","year":"2013","journal-title":"Nat Methods"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.celrep.2013.06.020","article-title":"Highly efficient targeted mutagenesis of Drosophila with the CRISPR\/Cas9 system","volume":"4","author":"AR Bassett","year":"2013","journal-title":"Cell Rep"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nbt.2501","article-title":"Efficient genome editing in zebrafish using a CRISPR-Cas system","volume":"31","author":"WY Hwang","year":"2013","journal-title":"Nat Biotechnol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.cell.2013.04.025","article-title":"One-step generation of mice carrying mutations in multiple genes by CRISPR\/Cas-mediated genome engineering","volume":"153","author":"H Wang","year":"2013","journal-title":"Cell"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.cell.2014.01.027","article-title":"Generation of gene-modified cynomolgus monkey via Cas9\/RNA-mediated gene targeting in one-cell embryos","volume":"156","author":"Y Niu","year":"2014","journal-title":"Cell"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"16526","DOI":"10.1073\/pnas.1310478110","article-title":"Efficient nonmeiotic allele introgression in livestock using custom endonucleases","volume":"110","author":"W Tan","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.cell.2014.09.014","article-title":"CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling","volume":"159","author":"RJ Platt","year":"2014","journal-title":"Cell"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"5105","DOI":"10.1038\/srep05105","article-title":"Adenoviral vector delivery of RNA-guided CRISPR\/Cas9 nuclease complexes induces targeted mutagenesis in a diverse array of human cells","volume":"4","author":"I Maggio","year":"2014","journal-title":"Sci Rep"},{"key":"ref40","article-title":"CRISPR-Cas9 mediated gene knockout in primary human airway epithelial cells reveals a pro-inflammatory role for MUC18","author":"HW Chu","year":"2015","journal-title":"Gene Ther"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nbt.2623","article-title":"High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells","volume":"31","author":"Y Fu","year":"2013","journal-title":"Nat Biotechnol. Nature Publishing Group"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nbt.2675","article-title":"CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering","volume":"31","author":"P Mali","year":"2013","journal-title":"Nat Biotechnol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.stem.2014.04.020","article-title":"Low incidence of Off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing","volume":"15","author":"A Veres","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/nbt.2889","article-title":"Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells","volume":"32","author":"X Wu","year":"2014","journal-title":"Nat Biotechnol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nbt.2916","article-title":"Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease","volume":"32","author":"C Kuscu","year":"2014","journal-title":"Nat Biotechnol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0182974","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T01:02:44Z","timestamp":1588986164000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0182974"}},"subtitle":[],"editor":[{"given":"Alfred S.","family":"Lewin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,8,11]]},"references-count":45,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0182974","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,11]]}}}