{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:11:48Z","timestamp":1790514708123,"version":"4.1.0"},"reference-count":88,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008510","name":"University of Maryland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ageing Research Reviews"],"published-print":{"date-parts":[[2021,9]]},"DOI":"10.1016\/j.arr.2021.101385","type":"journal-article","created":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T05:23:47Z","timestamp":1622870627000},"page":"101385","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":47,"special_numbering":"C","title":["Gene targeting techniques for Huntington\u2019s disease"],"prefix":"10.1016","volume":"70","author":[{"given":"Eric","family":"Fields","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Vaughan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepika","family":"Tripu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Shrout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Conway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Salib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Dhamsania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Jacobsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Woo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijing","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.arr.2021.101385_bib0005","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41586-019-1711-4","article-title":"Search-and-replace genome editing without double-strand breaks or donor DNA","volume":"576","author":"Anzalone","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.arr.2021.101385_bib0010","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/s41587-020-0561-9","article-title":"Genome editing with CRISPR\u2013Cas nucleases, base editors, transposases and prime editors","volume":"38","author":"Anzalone","year":"2020","journal-title":"Nat. Biotechnol."},{"issue":"19","key":"10.1016\/j.arr.2021.101385_bib0015","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1212\/01.wnl.0000334276.09729.0e","article-title":"Weight loss in Huntington disease increases with higher CAG repeat number","volume":"71","author":"Aziz","year":"2008","journal-title":"Neurology"},{"key":"10.1016\/j.arr.2021.101385_bib0020","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neuron.2005.06.005","article-title":"p53 Mediates Cellular Dysfunction and Behavioral Abnormalities in Huntington\u2019s Disease","volume":"47","author":"Bae","year":"2005","journal-title":"Neuron"},{"key":"10.1016\/j.arr.2021.101385_bib0025","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.neuron.2015.10.038","article-title":"RAN translation in huntington disease","volume":"88","author":"Ba\u00f1ez-Coronel","year":"2015","journal-title":"Neuron"},{"key":"10.1016\/j.arr.2021.101385_bib0030","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1126\/science.aax3338","article-title":"Huntington\u2019s disease alters human neurodevelopment","volume":"369","author":"Barnat","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.arr.2021.101385_bib0035","first-page":"1","article-title":"Huntington disease","volume":"1","author":"Bates","year":"2015","journal-title":"Nat. Rev. Dis. Primer"},{"key":"10.1016\/j.arr.2021.101385_bib0040","first-page":"1","article-title":"Drugging DNA damage repair pathways for trinucleotide repeat expansion diseases","author":"Benn","year":"2020","journal-title":"J. Huntingt. Dis."},{"key":"10.1016\/j.arr.2021.101385_bib0045","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev.pharmtox.010909.105654","article-title":"RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform","volume":"50","author":"Bennett","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.arr.2021.101385_bib0050","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.arr.2021.101385_bib0055","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1474-4422(19)30139-5","article-title":"Safety of the tau-directed monoclonal antibody BIIB092 in progressive supranuclear palsy: a randomised, placebo-controlled, multiple ascending dose phase 1b trial","volume":"18","author":"Boxer","year":"2019","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.arr.2021.101385_bib0060","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/ejhg.2017.125","article-title":"Haplotype-based stratification of Huntington\u2019s disease","volume":"25","author":"Chao","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.arr.2021.101385_bib0065","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007308","article-title":"Comparison of phasing strategies for whole human genomes","volume":"14","author":"Choi","year":"2018","journal-title":"PLoS Genet."},{"key":"10.1016\/j.arr.2021.101385_bib0070","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0171127","article-title":"The expanded CAG repeat in the huntingtin gene as target for therapeutic RNA modulation throughout the HD mouse brain","volume":"12","author":"Datson","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.arr.2021.101385_bib0075","doi-asserted-by":"crossref","first-page":"3473","DOI":"10.1523\/JNEUROSCI.22-09-03473.2002","article-title":"Lentiviral-mediated delivery of mutant huntingtin in the striatum of rats induces a selective neuropathology modulated by polyglutamine repeat size, huntingtin expression levels, and protein length","volume":"22","author":"de Almeida","year":"2002","journal-title":"J. Neurosci."},{"key":"10.1016\/j.arr.2021.101385_bib0080","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3389\/fphar.2019.00305","article-title":"Antisense oligonucleotide: basic concepts and therapeutic application in inflammatory bowel disease","volume":"10","author":"Di Fusco","year":"2019","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.arr.2021.101385_bib0085","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/81593","article-title":"Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice","volume":"26","author":"Dragatsis","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.arr.2021.101385_bib0090","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.arr.2021.101385_bib0095","first-page":"475","article-title":"Small changes, big impact: posttranslational modifications and function of huntingtin in Huntington disease","volume":"17","author":"Ehrnhoefer","year":"2011","journal-title":"Neurosci. Rev. J. Bringing Neurobiol. Neurol. Psychiatry"},{"key":"10.1016\/j.arr.2021.101385_bib0100","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.stemcr.2014.02.011","article-title":"Huntingtin regulates mammary stem cell division and differentiation","volume":"2","author":"Elias","year":"2014","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.arr.2021.101385_bib0105","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/nbt.2413","article-title":"Single-stranded siRNAs for in vivo gene silencing","volume":"30","author":"Elsner","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.arr.2021.101385_bib0110","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3727\/096368914X678454","article-title":"Polyglutamine (PolyQ) diseases: genetics to treatments","volume":"23","author":"Fan","year":"2014","journal-title":"Cell Transplant."},{"key":"10.1016\/j.arr.2021.101385_bib0115","doi-asserted-by":"crossref","first-page":"574","DOI":"10.3389\/fncel.2019.00574","article-title":"Altered Levels and Isoforms of Tau and Nuclear Membrane Invaginations in Huntington\u2019s Disease","volume":"13","author":"Fern\u00e1ndez-Nogales","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.arr.2021.101385_bib0120","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.tins.2013.01.005","article-title":"Gut\u2013brain axis: how the microbiome influences anxiety and depression","volume":"36","author":"Foster","year":"2013","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.arr.2021.101385_bib0125","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ebiom.2017.09.020","article-title":"Microbiota-related changes in bile acid & tryptophan metabolism are associated with gastrointestinal dysfunction in a mouse model of autism","volume":"24","author":"Golubeva","year":"2017","journal-title":"EBioMedicine"},{"key":"10.1016\/j.arr.2021.101385_bib0130","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1073\/pnas.1116053109","article-title":"Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease","volume":"109","author":"Greenblum","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.arr.2021.101385_bib0135","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.arr.2021.101385_bib0140","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1093\/brain\/awr333","article-title":"Six-month partial suppression of Huntingtin is well tolerated in the adult rhesus striatum","volume":"135","author":"Grondin","year":"2012","journal-title":"Brain"},{"key":"10.1016\/j.arr.2021.101385_bib0145","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2020.104958","article-title":"Why Woody got the blues: the neurobiology of depression in Huntington\u2019s disease","volume":"142","author":"Gubert","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.arr.2021.101385_bib0150","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/aps.2018.11","article-title":"Proteostasis in Huntington\u2019s disease: disease mechanisms and therapeutic opportunities","volume":"39","author":"Harding","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.arr.2021.101385_bib0155","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ydbio.2015.07.013","article-title":"Huntingtin is required for ciliogenesis and neurogenesis during early Xenopus development","volume":"408","author":"Haremaki","year":"2015","journal-title":"Dev. Biol."},{"key":"10.1016\/j.arr.2021.101385_bib0160","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/S1534-5807(02)00188-0","article-title":"The IGF-1\/Akt Pathway Is Neuroprotective in Huntington\u2019s Disease and Involves Huntingtin Phosphorylation by Akt","volume":"2","author":"Humbert","year":"2002","journal-title":"Dev. Cell"},{"key":"10.1016\/j.arr.2021.101385_bib0165","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nrm2321","article-title":"Argonaute proteins: key players in RNA silencing","volume":"9","author":"Hutvagner","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.arr.2021.101385_bib0170","series-title":"International Review of Neurobiology, Pathophysiology, Pharmacology, and Biochemistry of Dyskinesia","first-page":"373","article-title":"Pathogenic mechanisms in Huntington\u2019s disease","author":"Jones","year":"2011"},{"key":"10.1016\/j.arr.2021.101385_bib0175","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.1172\/JCI57552","article-title":"Ciliogenesis is regulated by a huntingtin-HAP1-PCM1 pathway and is altered in Huntington disease","volume":"121","author":"Keryer","year":"2011","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.arr.2021.101385_bib0180","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41586-020-03086-7","article-title":"In vivo base editing rescues Hutchinson\u2013Gilford progeria syndrome in mice","volume":"589","author":"Koblan","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.arr.2021.101385_bib0185","article-title":"Microbiome profiling reveals gut dysbiosis in a transgenic mouse model of Huntington\u2019s disease","volume":"135","author":"Kong","year":"2020","journal-title":"Neurobiol. Dis., Microbiome in neurological and psychiatric disease"},{"key":"10.1016\/j.arr.2021.101385_bib0190","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.arr.2021.101385_bib0195","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/sj.embor.7400250","article-title":"Huntingtin and the molecular pathogenesis of Huntington\u2019s disease","volume":"5","author":"Landles","year":"2004","journal-title":"EMBO Rep."},{"key":"10.1016\/j.arr.2021.101385_bib0200","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0378-1119(92)90121-5","article-title":"RNase H-mediated inhibition of translation by antisense oligodeoxyribo-nucleotides: use of backbone modification to improve specificity","volume":"121","author":"Larrouy","year":"1992","journal-title":"Gene"},{"key":"10.1016\/j.arr.2021.101385_bib0205","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1001\/jamaneurol.2020.0299","article-title":"Huntingtin-lowering therapies for huntington disease: a review of the evidence of potential benefits and risks","volume":"77","author":"Leavitt","year":"2020","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.arr.2021.101385_bib0210","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2020.105076","article-title":"Striatal circuit development and its alterations in Huntington\u2019s disease","volume":"145","author":"Lebouc","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.arr.2021.101385_bib0215","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1212\/WNL.0b013e318249f683","article-title":"CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion","volume":"78","author":"Lee","year":"2012","journal-title":"Neurology"},{"key":"10.1016\/j.arr.2021.101385_bib0220","doi-asserted-by":"crossref","first-page":"6106","DOI":"10.1128\/MCB.00420-09","article-title":"Mutant huntingtin impairs vesicle formation from recycling endosomes by interfering with Rab11 activity","volume":"29","author":"Li","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.arr.2021.101385_bib0225","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-019-1722-1","article-title":"Allele-selective lowering of mutant HTT protein by HTT\u2013LC3 linker compounds","volume":"575","author":"Li","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.arr.2021.101385_bib0230","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jns.2008.09.029","article-title":"Late onset huntington disease: clinical and genetic characteristics of 34 cases","volume":"276","author":"Lipe","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"10.1016\/j.arr.2021.101385_bib0235","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.neuron.2012.06.001","article-title":"\u201cHuntingtin Holiday\u201d: Progress toward an Antisense Therapy for Huntington\u2019s Disease","volume":"74","author":"Lu","year":"2012","journal-title":"Neuron"},{"key":"10.1016\/j.arr.2021.101385_bib0240","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1083\/jcb.200412071","article-title":"Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases implications for mutant huntingtin toxicity","volume":"169","author":"Luo","year":"2005","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.arr.2021.101385_bib0245","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3233\/JHD-200395","article-title":"Biological Aging and the Cellular Pathogenesis of Huntington\u2019s Disease","volume":"9","author":"Machiela","year":"2020","journal-title":"J. Huntingt. Dis."},{"key":"10.1016\/j.arr.2021.101385_bib0250","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.arr.2021.101385_bib0255","doi-asserted-by":"crossref","first-page":"8096","DOI":"10.1038\/s41598-018-25903-w","article-title":"A human huntingtin SNP alters post-translational modification and pathogenic proteolysis of the protein causing Huntington disease","volume":"8","author":"Martin","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2021.101385_bib0260","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.arr.2021.101385_bib0265","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 Vitro and In Vivo","volume":"25","author":"Monteys","year":"2017","journal-title":"Mol. Ther."},{"key":"10.1016\/j.arr.2021.101385_bib0270","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.arr.2021.101385_bib0275","series-title":"SNP Database [WWW Document]. dbSNP","author":"NCBI","year":"2021"},{"key":"10.1016\/j.arr.2021.101385_bib0280","doi-asserted-by":"crossref","DOI":"10.4081\/ni.2018.7473","article-title":"Cognitive impairment in neuromuscular diseases: a systematic review","volume":"10","author":"Orsini","year":"2018","journal-title":"Neurol. Int."},{"key":"10.1016\/j.arr.2021.101385_bib0285","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1136\/jnnp.71.3.310","article-title":"Neuropsychiatric aspects of Huntington\u2019s disease","volume":"71","author":"Paulsen","year":"2001","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"10.1016\/j.arr.2021.101385_bib0290","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0073902","article-title":"Huntingtin acts non cell-autonomously on hippocampal neurogenesis and controls anxiety-related behaviors in adult mouse","volume":"8","author":"Pla","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.arr.2021.101385_bib0295","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature11450","article-title":"A metagenome-wide association study of gut microbiota in type 2 diabetes","volume":"490","author":"Qin","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.arr.2021.101385_bib0300","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.trci.2018.10.007","article-title":"A randomized, single ascending dose study of intravenous BIIB092 in healthy participants","volume":"4","author":"Qureshi","year":"2018","journal-title":"Alzheimers Dement. Transl. Res. Clin. Interv."},{"key":"10.1016\/j.arr.2021.101385_bib0305","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.arr.2021.101385_bib0310","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3233\/JHD-189001","article-title":"Huntington\u2019s disease clinical trials corner: february 2018","volume":"7","author":"Rodrigues","year":"2018","journal-title":"J. Huntingt. Dis."},{"key":"10.1016\/j.arr.2021.101385_bib0315","doi-asserted-by":"crossref","first-page":"4319","DOI":"10.1172\/JCI83185","article-title":"Targeting CAG repeat RNAs reduces Huntington\u2019s disease phenotype independently of huntingtin levels","volume":"126","author":"Ru\u00e9","year":"2016","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.arr.2021.101385_bib0320","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1073\/pnas.1221891110","article-title":"Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease","volume":"110","author":"Sathasivam","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.arr.2021.101385_bib0325","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0092-8674(00)81782-1","article-title":"Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions","volume":"95","author":"Saudou","year":"1998","journal-title":"Cell"},{"key":"10.1016\/j.arr.2021.101385_bib0330","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/mds.26069","article-title":"Gut microbiota are related to Parkinson\u2019s disease and clinical phenotype","volume":"30","author":"Scheperjans","year":"2015","journal-title":"Mov. Disord."},{"key":"10.1016\/j.arr.2021.101385_bib0335","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/hmg\/8.3.397","article-title":"Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-Terminal fragment of huntingtin","volume":"8","author":"Schilling","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.arr.2021.101385_bib0340","first-page":"65","article-title":"The biological function of the Huntingtin protein and its relevance to Huntington\u2019s Disease pathology","volume":"5","author":"Schulte","year":"2011","journal-title":"Curr. Trends Neurol."},{"key":"10.1016\/j.arr.2021.101385_bib0345","doi-asserted-by":"crossref","first-page":"e323","DOI":"10.1212\/NXG.0000000000000323","article-title":"Antisense oligonucleotides: a primer","volume":"5","author":"Scoles","year":"2019","journal-title":"Neurol. Genet."},{"key":"10.1016\/j.arr.2021.101385_bib0350","first-page":"4566","article-title":"Permanent inactivation of Huntington\u2019s disease mutation by personalized allele-specific CRISPR\/Cas9","volume":"25","author":"Shin","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.arr.2021.101385_bib0355","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2020.105120","article-title":"Characterization of tau binding by gosuranemab","volume":"146","author":"Sopko","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.arr.2021.101385_bib0360","doi-asserted-by":"crossref","first-page":"13589","DOI":"10.1523\/JNEUROSCI.4286-09.2009","article-title":"Intrabody gene therapy ameliorates motor, cognitive, and neuropathological symptoms in multiple mouse models of Huntington\u2019s disease","volume":"29","author":"Southwell","year":"2009","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"10.1016\/j.arr.2021.101385_bib0365","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-75229-9","article-title":"Increased intestinal permeability and gut dysbiosis in the R6\/2 mouse model of Huntington\u2019s disease","volume":"10","author":"Stan","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2021.101385_bib0370","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1089\/hum.2013.200","article-title":"Silencing mutant huntingtin by adeno-associated virus-mediated RNA interference ameliorates disease manifestations in the YAC128 mouse model of huntington\u2019s disease","volume":"25","author":"Stanek","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.arr.2021.101385_bib0375","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1056\/NEJMoa1900907","article-title":"Targeting Huntingtin Expression in Patients with Huntington\u2019s Disease","volume":"380","author":"Tabrizi","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.arr.2021.101385_bib0380","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41582-020-0389-4","article-title":"Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities","volume":"16","author":"Tabrizi","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.arr.2021.101385_bib0385","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1083\/jcb.200909067","article-title":"IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome","volume":"187","author":"Thompson","year":"2009","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.arr.2021.101385_bib0390","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3233\/JHD-180331","article-title":"Transcriptional regulation of the huntingtin gene","volume":"7","author":"Thomson","year":"2018","journal-title":"J. Huntingt. Dis."},{"key":"10.1016\/j.arr.2021.101385_bib0395","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/nature05414","article-title":"An obesity-associated gut microbiome with increased capacity for energy harvest","volume":"444","author":"Turnbaugh","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.arr.2021.101385_bib0400","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3233\/JHD-200394","article-title":"The Neurodevelopmental Hypothesis of Huntington\u2019s Disease","volume":"9","author":"van der Plas","year":"2020","journal-title":"J. Huntingt. Dis."},{"key":"10.1016\/j.arr.2021.101385_bib0405","doi-asserted-by":"crossref","first-page":"13537","DOI":"10.1038\/s41598-017-13601-y","article-title":"Gut microbiome alterations in Alzheimer\u2019s disease","volume":"7","author":"Vogt","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2021.101385_bib0410","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","article-title":"Huntington\u2019s disease","volume":"369","author":"Walker","year":"2007","journal-title":"Lancet"},{"key":"10.1016\/j.arr.2021.101385_bib0415","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/nm.3514","article-title":"Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington\u2019s disease","volume":"20","author":"Wang","year":"2014","journal-title":"Nat. Med."},{"key":"10.1016\/j.arr.2021.101385_bib0420","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":"PNAS"},{"key":"10.1016\/j.arr.2021.101385_bib0425","doi-asserted-by":"crossref","DOI":"10.1093\/braincomms\/fcaa110","article-title":"Gut dysbiosis in Huntington\u2019s disease: associations among gut microbiota, cognitive performance and clinical outcomes","volume":"2","author":"Wasser","year":"2020","journal-title":"Brain Commun"},{"key":"10.1016\/j.arr.2021.101385_bib0430","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S1474-4422(17)30280-6","article-title":"Therapies targeting DNA and RNA in Huntington\u2019s disease","volume":"16","author":"Wild","year":"2017","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.arr.2021.101385_bib0435","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1093\/hmg\/11.23.2905","article-title":"Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells","volume":"11","author":"Yang","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.arr.2021.101385_bib0440","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.cell.2012.08.002","article-title":"Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression","volume":"150","author":"Yu","year":"2012","journal-title":"Cell"}],"container-title":["Ageing Research Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S156816372100132X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S156816372100132X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T19:02:22Z","timestamp":1761591742000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S156816372100132X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":88,"alternative-id":["S156816372100132X"],"URL":"https:\/\/doi.org\/10.1016\/j.arr.2021.101385","relation":{},"ISSN":["1568-1637"],"issn-type":[{"value":"1568-1637","type":"print"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Gene targeting techniques for Huntington\u2019s disease","name":"articletitle","label":"Article Title"},{"value":"Ageing Research Reviews","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.arr.2021.101385","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"101385"}}