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Lett."},{"key":"10.1016\/j.neuron.2019.01.039_bib82","doi-asserted-by":"crossref","first-page":"5868","DOI":"10.1073\/pnas.0801775105","article-title":"Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi","volume":"105","author":"McBride","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2019.01.039_bib83","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. 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Ther. Nucleic Acids"},{"key":"10.1016\/j.neuron.2019.01.039_bib88","doi-asserted-by":"crossref","first-page":"9607","DOI":"10.1073\/pnas.0902420106","article-title":"Zinc-finger directed double-strand breaks within CAG repeat tracts promote repeat instability in human cells","volume":"106","author":"Mittelman","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2019.01.039_bib89","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. 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SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy","volume":"345","author":"Naryshkin","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.neuron.2019.01.039_bib93","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.neuron.2019.01.039_bib94","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1038\/s41598-017-01510-z","article-title":"The pathogenic exon 1 HTT protein is produced by incomplete splicing in Huntington\u2019s disease patients","volume":"7","author":"Neueder","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuron.2019.01.039_bib95","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1002\/hbm.23921","article-title":"Stimulating neural plasticity with real-time fMRI neurofeedback in\u00a0Huntington\u2019s disease: a proof of concept study","volume":"39","author":"Papoutsi","year":"2018","journal-title":"Hum. Brain Mapp."},{"key":"10.1016\/j.neuron.2019.01.039_bib96","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.cub.2009.03.030","article-title":"Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington\u2019s disease patients","volume":"19","author":"Pfister","year":"2009","journal-title":"Curr. Biol."},{"key":"10.1016\/j.neuron.2019.01.039_bib97","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/nrn3570","article-title":"Choosing an animal model for the study of Huntington\u2019s disease","volume":"14","author":"Pouladi","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.neuron.2019.01.039_bib98","unstructured":"PTC Therapeutics (2017). RG7916 Increased SMN Protein Production in SUNFISH clinical trial in patients with type 2\/3 spinal muscular atrophy. http:\/\/ir.ptcbio.com\/news-releases\/news-release-details\/rg7916-increased-smn-protein-production-sunfish-clinical-trial."},{"key":"10.1016\/j.neuron.2019.01.039_bib99","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1001\/jamaneurol.2018.0233","article-title":"Adeno-associated viral vector (Serotype 2)-nerve growth factor for patients with Alzheimer disease: a randomized clinical trial","volume":"75","author":"Rafii","year":"2018","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.neuron.2019.01.039_bib100","doi-asserted-by":"crossref","first-page":"10855","DOI":"10.1074\/jbc.M804813200","article-title":"Mutant huntingtin N-terminal fragments of specific size mediate aggregation and toxicity in neuronal cells","volume":"284","author":"Ratovitski","year":"2009","journal-title":"J.\u00a0Biol. 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FDA approves first drug for\u00a0spinal\u00a0muscular atrophy. https:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm534611.htm."},{"key":"10.1016\/j.neuron.2019.01.039_bib130","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1093\/hmg\/ddi147","article-title":"Loss of wild-type huntingtin influences motor dysfunction and survival in the YAC128 mouse model of Huntington disease","volume":"14","author":"Van Raamsdonk","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.neuron.2019.01.039_bib131","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.neures.2005.06.021","article-title":"Clinico-pathological rescue of a model mouse of Huntington\u2019s disease by siRNA","volume":"53","author":"Wang","year":"2005","journal-title":"Neurosci. 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