{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:19:21Z","timestamp":1791314361516,"version":"4.3.1"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,4,11]],"date-time":"2014-04-11T00:00:00Z","timestamp":1397174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:p>Gene silencing offers a novel therapeutic strategy for dominant genetic disorders. In specific diseases, selective silencing of only one copy of a gene may be advantageous over non\u2010selective silencing of both copies. Huntington disease (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>) is an autosomal dominant disorder caused by an expanded <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content> trinucleotide repeat in the Huntingtin gene (<jats:italic><jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content><\/jats:italic>). Silencing both expanded and normal copies of <jats:italic><jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content><\/jats:italic> may be therapeutically beneficial, but preservation of normal <jats:italic><jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content><\/jats:italic> expression is preferred. Allele\u2010specific methods can selectively silence the mutant <jats:italic><jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content><\/jats:italic> transcript by targeting either the expanded <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content> repeat or single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNPs<\/jats:styled-content>) in linkage disequilibrium with the expansion. Both approaches require personalized treatment strategies based on patient genotypes. We compare the prospect of safe treatment of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> by <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content>\u2010 and <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>\u2010specific silencing approaches and review <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> population genetics used to guide target identification in the patient population. Clinical implementation of allele\u2010specific <jats:italic><jats:styled-content style=\"fixed-case\">HTT<\/jats:styled-content><\/jats:italic> silencing faces challenges common to personalized genetic medicine, requiring novel solutions from clinical scientists and regulatory authorities.<\/jats:p>","DOI":"10.1111\/cge.12385","type":"journal-article","created":{"date-parts":[[2014,3,19]],"date-time":"2014-03-19T16:07:52Z","timestamp":1395245272000},"page":"29-36","source":"Crossref","is-referenced-by-count":49,"title":["Personalized gene silencing therapeutics for Huntington disease"],"prefix":"10.1111","volume":"86","author":[{"given":"C.","family":"Kay","sequence":"first","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.H.","family":"Skotte","sequence":"additional","affiliation":[{"name":"Centre for Molecular 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