{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:16:30Z","timestamp":1791303390208,"version":"4.1.0"},"reference-count":88,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Ruth L. Kirschstein National Research Service Award","award":["F32GM113446"],"award-info":[{"award-number":["F32GM113446"]}]},{"DOI":"10.13039\/100001441","name":"Judith and Jean Pape Adams Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001441","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NSF"},{"DOI":"10.13039\/100006978","name":"UC Berkeley","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006978","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01EY022975"],"award-info":[{"award-number":["R01EY022975"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy - Nucleic Acids"],"published-print":{"date-parts":[[2019,9]]},"DOI":"10.1016\/j.omtn.2019.07.009","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T00:42:32Z","timestamp":1564101752000},"page":"829-839","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":161,"special_numbering":"C","title":["CRISPR-Cas9-Mediated Genome Editing Increases Lifespan and Improves Motor Deficits in a Huntington\u2019s Disease Mouse Model"],"prefix":"10.1016","volume":"17","author":[{"given":"Freja K.","family":"Ekman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Ojala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maroof M.","family":"Adil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola A.","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David V.","family":"Schaffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtn.2019.07.009_bib1","doi-asserted-by":"crossref","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington disease","volume":"1","author":"Bates","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.omtn.2019.07.009_bib2","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes","volume":"72","author":"MacDonald","year":"1993","journal-title":"Cell"},{"key":"10.1016\/j.omtn.2019.07.009_bib3","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1523\/JNEUROSCI.19-07-02522.1999","article-title":"Nuclear and neuropil aggregates in Huntington\u2019s disease: relationship to neuropathology","volume":"19","author":"Gutekunst","year":"1999","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.omtn.2019.07.009_bib4","doi-asserted-by":"crossref","first-page":"12784","DOI":"10.1073\/pnas.221451398","article-title":"Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington\u2019s disease brains, associate with membranes, and undergo calpain-dependent proteolysis","volume":"98","author":"Kim","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtn.2019.07.009_bib5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.neuron.2017.03.023","article-title":"Mutant huntingtin disrupts the nuclear pore complex","volume":"94","author":"Grima","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.omtn.2019.07.009_bib6","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","article-title":"Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain","volume":"277","author":"DiFiglia","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.omtn.2019.07.009_bib7","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0092-8674(00)80514-0","article-title":"Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in\u00a0vitro and in\u00a0vivo","volume":"90","author":"Scherzinger","year":"1997","journal-title":"Cell"},{"key":"10.1016\/j.omtn.2019.07.009_bib8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/7854_2014_354","article-title":"The neuropathology of Huntington\u2019s disease","volume":"22","author":"Waldvogel","year":"2015","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"10.1016\/j.omtn.2019.07.009_bib9","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1097\/00005072-198511000-00003","article-title":"Neuropathological classification of Huntington\u2019s disease","volume":"44","author":"Vonsattel","year":"1985","journal-title":"J.\u00a0Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.omtn.2019.07.009_bib10","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nrneurol.2014.24","article-title":"Huntington disease: natural history, biomarkers and prospects for therapeutics","volume":"10","author":"Ross","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.omtn.2019.07.009_bib11","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.omtn.2019.07.009_bib12","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.omtn.2019.07.009_bib13","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.omtn.2019.07.009_bib14","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.omtn.2019.07.009_bib15","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.omtn.2019.07.009_bib16","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1038\/mt.2011.201","article-title":"Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene \/ allele-specific silencing of mutant huntingtin","volume":"19","author":"Carroll","year":"2011","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtn.2019.07.009_bib17","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.molmed.2012.09.001","article-title":"Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases","volume":"18","author":"Southwell","year":"2012","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.omtn.2019.07.009_bib18","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.omtn.2019.07.009_bib19","doi-asserted-by":"crossref","first-page":"e99341","DOI":"10.1371\/journal.pone.0099341","article-title":"Allele-specific silencing of mutant huntingtin in rodent brain and human stem cells","volume":"9","author":"Drouet","year":"2014","journal-title":"PLoS ONE"},{"key":"10.1016\/j.omtn.2019.07.009_bib20","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/gt.2017.71","article-title":"AAV5-miHTT gene therapy demonstrates suppression of mutant huntingtin aggregation and neuronal dysfunction in a rat model of Huntington\u2019s disease","volume":"24","author":"Miniarikova","year":"2017","journal-title":"Gene Ther."},{"key":"10.1016\/j.omtn.2019.07.009_bib21","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1016\/j.ymthe.2018.06.021","article-title":"AAV5-miHTT gene therapy demonstrates broad distribution and strong human mutant huntingtin lowering in a Huntington\u2019s sisease minipig model","volume":"26","author":"Evers","year":"2018","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtn.2019.07.009_bib22","doi-asserted-by":"crossref","first-page":"e297","DOI":"10.1038\/mtna.2016.7","article-title":"Design, characterization, and lead selection of therapeutic miRNAs targeting huntingtin for development of gene therapy for huntington\u2019s disease","volume":"5","author":"Miniarikova","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.omtn.2019.07.009_bib23","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":"Jackson","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtn.2019.07.009_bib24","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1261\/rna.25706","article-title":"Widespread siRNA \u201coff-target\u201d transcript silencing mediated by seed region sequence complementarity","volume":"12","author":"Jackson","year":"2006","journal-title":"RNA"},{"key":"10.1016\/j.omtn.2019.07.009_bib25","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1007\/s11095-011-0608-1","article-title":"Subcellular fate and off-target effects of siRNA, shRNA, and miRNA","volume":"28","author":"Singh","year":"2011","journal-title":"Pharm. Res."},{"key":"10.1016\/j.omtn.2019.07.009_bib26","doi-asserted-by":"crossref","first-page":"a023754","DOI":"10.1101\/cshperspect.a023754","article-title":"Genome-editing technologies: principles and applications","volume":"8","author":"Gaj","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.omtn.2019.07.009_bib27","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.omtn.2019.07.009_bib28","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.omtn.2019.07.009_bib29","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.omtn.2019.07.009_bib30","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.omtn.2019.07.009_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.omtn.2019.07.009_bib32","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/mt.2016.10","article-title":"Genome-editing technologies for gene and cell therapy","volume":"24","author":"Maeder","year":"2016","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtn.2019.07.009_bib33","doi-asserted-by":"crossref","first-page":"5809","DOI":"10.1073\/pnas.0800940105","article-title":"Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases","volume":"105","author":"Santiago","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtn.2019.07.009_bib34","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0092-8674(00)80542-5","article-title":"A perfect message: RNA surveillance and nonsense-mediated decay","volume":"96","author":"Hentze","year":"1999","journal-title":"Cell"},{"key":"10.1016\/j.omtn.2019.07.009_bib35","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1177\/1073858414521870","article-title":"Adeno-associated virus vectors and neurological gene therapy","volume":"21","author":"Ojala","year":"2015","journal-title":"Neuroscientist"},{"key":"10.1016\/j.omtn.2019.07.009_bib36","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.nbd.2011.09.014","article-title":"Viral vectors for gene delivery to the central nervous system","volume":"48","author":"Lentz","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.omtn.2019.07.009_bib37","doi-asserted-by":"crossref","first-page":"e76310","DOI":"10.1371\/journal.pone.0076310","article-title":"Analysis of transduction efficiency, tropism and axonal transport of AAV serotypes 1, 2, 5, 6, 8 and 9 in the mouse brain","volume":"8","author":"Aschauer","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1016\/j.omtn.2019.07.009_bib38","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/mt.2015.151","article-title":"Genome engineering using adeno-associated virus: basic and clinical research applications","volume":"24","author":"Gaj","year":"2016","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtn.2019.07.009_bib39","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.omtn.2019.07.009_bib40","doi-asserted-by":"crossref","first-page":"13986","DOI":"10.1073\/pnas.0906463106","article-title":"Accumulation of ubiquitin conjugates in a polyglutamine disease model occurs without global ubiquitin\/proteasome system impairment","volume":"106","author":"Maynard","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtn.2019.07.009_bib41","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","article-title":"Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice","volume":"87","author":"Mangiarini","year":"1996","journal-title":"Cell"},{"key":"10.1016\/j.omtn.2019.07.009_bib42","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/ng.2202","article-title":"Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration","volume":"44","author":"Chiang","year":"2012","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtn.2019.07.009_bib43","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.nbd.2009.05.007","article-title":"Systematic behavioral evaluation of Huntington\u2019s disease transgenic and knock-in mouse models","volume":"35","author":"Menalled","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.omtn.2019.07.009_bib44","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1152\/jn.00762.2011","article-title":"A critical window of CAG repeat-length correlates with phenotype severity in the R6\/2 mouse model of Huntington\u2019s disease","volume":"107","author":"Cummings","year":"2012","journal-title":"J.\u00a0Neurophysiol."},{"key":"10.1016\/j.omtn.2019.07.009_bib45","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1038\/nbt1362","article-title":"Identification and targeting of the ROSA26 locus in human embryonic stem cells","volume":"25","author":"Irion","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtn.2019.07.009_bib46","doi-asserted-by":"crossref","first-page":"eaar3952","DOI":"10.1126\/sciadv.aar3952","article-title":"In\u00a0vivo genome editing improves motor function and extends survival in a mouse model of ALS","volume":"3","author":"Gaj","year":"2017","journal-title":"Sci. Adv."},{"key":"10.1016\/j.omtn.2019.07.009_bib47","doi-asserted-by":"crossref","first-page":"16037","DOI":"10.1038\/mtm.2016.37","article-title":"Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington\u2019s disease","volume":"3","author":"Hadaczek","year":"2016","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtn.2019.07.009_bib48","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/gt.2015.113","article-title":"AAV1\/2-mediated BDNF gene therapy in a transgenic rat model of Huntington\u2019s disease","volume":"23","author":"Connor","year":"2016","journal-title":"Gene Ther."},{"key":"10.1016\/j.omtn.2019.07.009_bib49","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/mt.2008.50","article-title":"AAV vector-mediated RNAi of mutant huntingtin expression is neuroprotective in a novel genetic rat model of Huntington\u2019s disease","volume":"16","author":"Franich","year":"2008","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtn.2019.07.009_bib50","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1083\/jcb.200710158","article-title":"Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin","volume":"181","author":"Wang","year":"2008","journal-title":"J.\u00a0Cell Biol."},{"key":"10.1016\/j.omtn.2019.07.009_bib51","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/nbt.3583","article-title":"Analyzing CRISPR genome-editing experiments with CRISPResso","volume":"34","author":"Pinello","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtn.2019.07.009_bib52","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.omtn.2019.07.009_bib53","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1023\/A:1010887421592","article-title":"Progressive formation of inclusions in the striatum and hippocampus of mice transgenic for the human Huntington\u2019s disease mutation","volume":"29","author":"Morton","year":"2000","journal-title":"J.\u00a0Neurocytol."},{"key":"10.1016\/j.omtn.2019.07.009_bib54","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/cne.10295","article-title":"Cellular localization and development of neuronal intranuclear inclusions in striatal and cortical neurons in R6\/2 transgenic mice","volume":"449","author":"Meade","year":"2002","journal-title":"J.\u00a0Comp. Neurol."},{"key":"10.1016\/j.omtn.2019.07.009_bib55","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1242\/dmm.002451","article-title":"Mouse models of Huntington disease: variations on a theme","volume":"2","author":"Ehrnhoefer","year":"2009","journal-title":"Dis. Model. Mech."},{"key":"10.1016\/j.omtn.2019.07.009_bib56","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000443738","article-title":"The prevalence of Huntington\u2019s disease","volume":"46","author":"Rawlins","year":"2016","journal-title":"Neuroepidemiology"},{"key":"10.1016\/j.omtn.2019.07.009_bib57","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.neuron.2016.09.021","article-title":"A designer AAV variant permits efficient retrograde access to projection neurons","volume":"92","author":"Tervo","year":"2016","journal-title":"Neuron"},{"key":"10.1016\/j.omtn.2019.07.009_bib58","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nbt.3055","article-title":"In\u00a0vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9","volume":"33","author":"Swiech","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtn.2019.07.009_bib59","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1172\/JCI92087","article-title":"CRISPR\/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington\u2019s disease","volume":"127","author":"Yang","year":"2017","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.omtn.2019.07.009_bib60","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ymthe.2016.11.010","article-title":"CRISPR\/Cas9 editing of the mutant huntingtin allele in\u00a0vitro and in\u00a0vivo","volume":"25","author":"Monteys","year":"2017","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtn.2019.07.009_bib61","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1016\/j.celrep.2017.08.075","article-title":"The self-inactivating KamiCas9 system for the editing of CNS disease genes","volume":"20","author":"Merienne","year":"2017","journal-title":"Cell Rep."},{"key":"10.1016\/j.omtn.2019.07.009_bib62","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nature20565","article-title":"In\u00a0vivo genome editing via CRISPR\/Cas9 mediated homology-independent targeted integration","volume":"540","author":"Suzuki","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.omtn.2019.07.009_bib63","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.bbadis.2009.04.001","article-title":"Mouse models of Huntington\u2019s disease and methodological considerations for therapeutic trials","volume":"1792","author":"Ferrante","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.omtn.2019.07.009_bib64","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/0092-8674(95)90542-1","article-title":"Targeted disruption of the Huntington\u2019s disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes","volume":"81","author":"Nasir","year":"1995","journal-title":"Cell"},{"key":"10.1016\/j.omtn.2019.07.009_bib65","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1126\/science.7618107","article-title":"Inactivation of the mouse Huntington\u2019s disease gene homolog Hdh","volume":"269","author":"Duyao","year":"1995","journal-title":"Science"},{"key":"10.1016\/j.omtn.2019.07.009_bib66","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.omtn.2019.07.009_bib67","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.omtn.2019.07.009_bib68","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/j.1471-4159.2010.06672.x","article-title":"Differential vulnerability of neurons in Huntington\u2019s disease: the role of cell type-specific features","volume":"113","author":"Han","year":"2010","journal-title":"J.\u00a0Neurochem."},{"key":"10.1016\/j.omtn.2019.07.009_bib69","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrg3742","article-title":"Engineering adeno-associated viruses for clinical gene therapy","volume":"15","author":"Kotterman","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.omtn.2019.07.009_bib70","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1056\/NEJMoa1407309","article-title":"Long-term safety and efficacy of factor IX gene therapy in hemophilia B","volume":"371","author":"Nathwani","year":"2014","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.omtn.2019.07.009_bib71","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/S0140-6736(13)62117-0","article-title":"Retinal gene therapy in patients with choroideremia: initial findings from a phase 1\/2 clinical trial","volume":"383","author":"MacLaren","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.omtn.2019.07.009_bib72","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1161\/ATVBAHA.108.175620","article-title":"Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients","volume":"28","author":"Stroes","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.omtn.2019.07.009_bib73","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1210\/jc.2011-3002","article-title":"Effect of alipogene tiparvovec (AAV1-LPL(S447X)) on postprandial chylomicron metabolism in lipoprotein lipase-deficient patients","volume":"97","author":"Carpentier","year":"2012","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.omtn.2019.07.009_bib74","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1056\/NEJMoa0802268","article-title":"Effect of gene therapy on visual function in Leber\u2019s congenital amaurosis","volume":"358","author":"Bainbridge","year":"2008","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.omtn.2019.07.009_bib75","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.omtn.2019.07.009_bib76","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/nbt.3026","article-title":"Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation","volume":"32","author":"Doench","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtn.2019.07.009_bib77","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.omtn.2019.07.009_bib78","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nbt.2909","article-title":"Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification","volume":"32","author":"Guilinger","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtn.2019.07.009_bib79","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nbt.2908","article-title":"Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing","volume":"32","author":"Tsai","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtn.2019.07.009_bib80","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1038\/mt.2016.172","article-title":"A self-restricted CRISPR system to reduce off-target effects","volume":"24","author":"Chen","year":"2016","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtn.2019.07.009_bib81","doi-asserted-by":"crossref","first-page":"15334","DOI":"10.1038\/ncomms15334","article-title":"Hit and go CAS9 delivered through a lentiviral based self-limiting circuit","volume":"8","author":"Petris","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.omtn.2019.07.009_bib82","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.omtn.2019.07.009_bib83","doi-asserted-by":"crossref","DOI":"10.1038\/nmeth.3284","article-title":"Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"10.1016\/j.omtn.2019.07.009_bib84","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"},{"key":"10.1016\/j.omtn.2019.07.009_bib85","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.stemcr.2018.03.007","article-title":"hPSC-derived striatal cells generated using a scalable 3D hydrogel promote recovery in a Huntington disease mouse model","volume":"10","author":"Adil","year":"2018","journal-title":"Stem Cell Reports"},{"key":"10.1016\/j.omtn.2019.07.009_bib86","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.stemcr.2017.11.005","article-title":"Human neural stem cell transplantation rescues functional deficits in R6\/2 and Q140 Huntington\u2019s disease mice","volume":"10","author":"Reidling","year":"2018","journal-title":"Stem Cell Reports"},{"key":"10.1016\/j.omtn.2019.07.009_bib87","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.copbio.2018.03.007","article-title":"Innovations in CRISPR technology","volume":"52","author":"Brooks","year":"2018","journal-title":"Curr. Opin. Biotechnol."},{"key":"10.1016\/j.omtn.2019.07.009_bib88","doi-asserted-by":"crossref","DOI":"10.1101\/pdb.prot086868","article-title":"Adeno-associated virus-mediated delivery of CRISPR-Cas systems for genome engineering in mammalian cells","volume":"2016","author":"Gaj","year":"2016","journal-title":"Cold Spring Harb. Protoc."}],"container-title":["Molecular Therapy - Nucleic Acids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2162253119301994?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2162253119301994?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T15:39:02Z","timestamp":1717688342000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2162253119301994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9]]},"references-count":88,"alternative-id":["S2162253119301994"],"URL":"https:\/\/doi.org\/10.1016\/j.omtn.2019.07.009","relation":{},"ISSN":["2162-2531"],"issn-type":[{"value":"2162-2531","type":"print"}],"subject":[],"published":{"date-parts":[[2019,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"CRISPR-Cas9-Mediated Genome Editing Increases Lifespan and Improves Motor Deficits in a Huntington\u2019s Disease Mouse Model","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy - Nucleic Acids","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtn.2019.07.009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors.","name":"copyright","label":"Copyright"}]}}