{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:56:24Z","timestamp":1792788984871,"version":"4.5.0"},"reference-count":44,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T00:00:00Z","timestamp":1479686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Hoppy\u2019s Hope Foundation","id":[{"id":"https:\/\/ror.org\/05wf1w785","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Philly Cure HD"},{"name":"The Leslie Gehry Brenner Prize"},{"name":"The Foerderer Grant for Excellence"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NS084475"],"award-info":[{"award-number":["NS084475"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NS076631"],"award-info":[{"award-number":["NS076631"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Children\u2019s Hospital of Philadelphia Research Institute","id":[{"id":"https:\/\/ror.org\/01z7r7q48","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2017,1]]},"DOI":"10.1016\/j.ymthe.2016.11.010","type":"journal-article","created":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T16:44:48Z","timestamp":1483634688000},"page":"12-23","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":305,"title":["CRISPR\/Cas9 Editing of the Mutant Huntingtin Allele In\u00a0Vitro and In\u00a0Vivo"],"prefix":"10.1016","volume":"25","author":[{"given":"Alex Mas","family":"Monteys","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shauna A.","family":"Ebanks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan S.","family":"Keiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly L.","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2016.11.010_bib1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1055\/s-2007-971176","article-title":"Huntington\u2019s disease","volume":"27","author":"Walker","year":"2007","journal-title":"Semin. Neurol."},{"key":"10.1016\/j.ymthe.2016.11.010_bib2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1089\/neu.1993.10.405","article-title":"Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus","volume":"10","author":"Hicks","year":"1993","journal-title":"J.\u00a0Neurotrauma"},{"issue":"R1","key":"10.1016\/j.ymthe.2016.11.010_bib3","doi-asserted-by":"crossref","first-page":"R98","DOI":"10.1093\/hmg\/ddq148","article-title":"Huntington\u2019s disease: progress toward effective disease-modifying treatments and a cure","volume":"19","author":"Johnson","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ymthe.2016.11.010_bib4","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)80623-6","article-title":"Reversal of neuropathology and motor dysfunction in a conditional model of Huntington\u2019s disease","volume":"101","author":"Yamamoto","year":"2000","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2016.11.010_bib5","doi-asserted-by":"crossref","first-page":"9773","DOI":"10.1523\/JNEUROSCI.3183-05.2005","article-title":"Full motor recovery despite striatal neuron loss and formation of irreversible amyloid-like inclusions in a conditional mouse model of Huntington\u2019s disease","volume":"25","author":"D\u00edaz-Hern\u00e1ndez","year":"2005","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.ymthe.2016.11.010_bib6","doi-asserted-by":"crossref","first-page":"5820","DOI":"10.1073\/pnas.0501507102","article-title":"RNA interference improves motor and neuropathological abnormalities in a Huntington\u2019s disease mouse model","volume":"102","author":"Harper","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2016.11.010_bib7","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/mt.2009.17","article-title":"Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington\u2019s disease mice","volume":"17","author":"Boudreau","year":"2009","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2016.11.010_bib8","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/ana.21569","article-title":"Sustained effects of nonallele-specific Huntingtin silencing","volume":"65","author":"Drouet","year":"2009","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.ymthe.2016.11.010_bib9","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.neuron.2012.05.009","article-title":"Sustained therapeutic reversal of Huntington\u2019s disease by transient repression of huntingtin synthesis","volume":"74","author":"Kordasiewicz","year":"2012","journal-title":"Neuron"},{"key":"10.1016\/j.ymthe.2016.11.010_bib10","doi-asserted-by":"crossref","first-page":"E3136","DOI":"10.1073\/pnas.1206506109","article-title":"Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6\/2 mice","volume":"109","author":"Garriga-Canut","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2016.11.010_bib11","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":"Jinek","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2016.11.010_bib12","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.1232033","article-title":"RNA-guided human genome engineering via Cas9","volume":"339","author":"Mali","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2016.11.010_bib13","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2016.11.010_bib14","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Ran","year":"2013","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.ymthe.2016.11.010_bib15","doi-asserted-by":"crossref","first-page":"e00471","DOI":"10.7554\/eLife.00471","article-title":"RNA-programmed genome editing in human cells","volume":"2","author":"Jinek","year":"2013","journal-title":"eLife"},{"key":"10.1016\/j.ymthe.2016.11.010_bib16","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00041.2009","article-title":"Molecular mechanisms and potential therapeutical targets in Huntington\u2019s disease","volume":"90","author":"Zuccato","year":"2010","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ymthe.2016.11.010_bib17","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nature13011","article-title":"DNA interrogation by the CRISPR RNA-guided endonuclease Cas9","volume":"507","author":"Sternberg","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2016.11.010_bib18","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":"Fu","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2016.11.010_bib19","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":"Kuscu","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2016.11.010_bib20","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nature13579","article-title":"Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease","volume":"513","author":"Anders","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2016.11.010_bib21","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature14592","article-title":"Engineered CRISPR-Cas9 nucleases with altered PAM specificities","volume":"523","author":"Kleinstiver","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2016.11.010_bib22","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nbt.3117","article-title":"GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases","volume":"33","author":"Tsai","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2016.11.010_bib23","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.cell.2015.09.038","article-title":"Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system","volume":"163","author":"Zetsche","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2016.11.010_bib24","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature14299","article-title":"In\u00a0vivo genome editing using Staphylococcus aureus Cas9","volume":"520","author":"Ran","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2016.11.010_bib25","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1093\/hmg\/7.5.791","article-title":"Functional analysis of the Huntington\u2019s disease (HD) gene promoter","volume":"7","author":"Coles","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ymthe.2016.11.010_bib26","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/nbt.2647","article-title":"DNA targeting specificity of RNA-guided Cas9 nucleases","volume":"31","author":"Hsu","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2016.11.010_bib27","doi-asserted-by":"crossref","first-page":"5405","DOI":"10.1038\/srep05405","article-title":"Comparison of non-canonical PAMs for CRISPR\/Cas9-mediated DNA cleavage in human cells","volume":"4","author":"Zhang","year":"2014","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2016.11.010_bib28","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/nmeth.3543","article-title":"CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in\u00a0vivo","volume":"12","author":"Moreno-Mateos","year":"2015","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2016.11.010_bib29","doi-asserted-by":"crossref","first-page":"16889","DOI":"10.1073\/pnas.1420103111","article-title":"Potential function for the Huntingtin protein as a scaffold for selective autophagy","volume":"111","author":"Ochaba","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2016.11.010_bib30","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.15252\/embj.201490808","article-title":"Huntingtin proteolysis releases non-polyQ fragments that cause toxicity through dynamin 1 dysregulation","volume":"34","author":"El-Daher","year":"2015","journal-title":"EMBO J."},{"key":"10.1016\/j.ymthe.2016.11.010_bib31","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nbt.2507","article-title":"Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease","volume":"31","author":"Cho","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2016.11.010_bib32","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1093\/bioinformatics\/btu048","article-title":"Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases","volume":"30","author":"Bae","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ymthe.2016.11.010_bib33","doi-asserted-by":"crossref","first-page":"6182","DOI":"10.1523\/JNEUROSCI.0857-08.2008","article-title":"Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice","volume":"28","author":"Gray","year":"2008","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.ymthe.2016.11.010_bib34","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1016\/j.cell.2013.08.021","article-title":"Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity","volume":"154","author":"Ran","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2016.11.010_bib35","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1038\/mt.2011.219","article-title":"Preclinical safety of RNAi-mediated HTT suppression in the rhesus macaque as a potential therapy for Huntington\u2019s disease","volume":"19","author":"McBride","year":"2011","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2016.11.010_bib36","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.1073\/pnas.1524575113","article-title":"Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis","volume":"113","author":"Wang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2016.11.010_bib37","doi-asserted-by":"crossref","first-page":"e0144970","DOI":"10.1371\/journal.pone.0144970","article-title":"Exploiting the CRISPR\/Cas9 PAM constraint for single-nucleotide resolution interventions","volume":"11","author":"Li","year":"2016","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ymthe.2016.11.010_bib38","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/gt.2015.82","article-title":"CRISPR\/Cas9 DNA cleavage at SNP-derived PAM enables both in\u00a0vitro and in\u00a0vivo KRT12 mutation-specific targeting","volume":"23","author":"Courtney","year":"2016","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2016.11.010_bib39","doi-asserted-by":"crossref","DOI":"10.1093\/hmg\/ddw286","article-title":"Permanent inactivation of Huntington\u2019s disease mutation by personalized allele-specific CRISPR\/Cas9","author":"Shin","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ymthe.2016.11.010_bib40","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/nbt.3290","article-title":"Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells","volume":"33","author":"Hendel","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2016.11.010_bib41","doi-asserted-by":"crossref","first-page":"E7110","DOI":"10.1073\/pnas.1520883112","article-title":"Synthetic CRISPR RNA-Cas9-guided genome editing in human cells","volume":"112","author":"Rahdar","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2016.11.010_bib42","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nbt.2808","article-title":"Improving CRISPR-Cas nuclease specificity using truncated guide RNAs","volume":"32","author":"Fu","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2016.11.010_bib43","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nature16526","article-title":"High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects","volume":"529","author":"Kleinstiver","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2016.11.010_bib44","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.aad5227","article-title":"Rationally engineered Cas9 nucleases with improved specificity","volume":"351","author":"Slaymaker","year":"2016","journal-title":"Science"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001616453931?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001616453931?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T11:49:50Z","timestamp":1601293790000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001616453931"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["S1525001616453931"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2016.11.010","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2017,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"CRISPR\/Cas9 Editing of the Mutant Huntingtin Allele In\u00a0Vitro and In\u00a0Vivo","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2016.11.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 The Author(s).","name":"copyright","label":"Copyright"}]}}