{"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":1791314361904,"version":"4.3.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2016,11,10]],"date-time":"2016-11-10T00:00:00Z","timestamp":1478736000000},"content-version":"vor","delay-in-days":1154,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Huntington\u2019s disease (HD) is a neurodegenerative genetic disorder caused by the expansion of the CAG repeat in the translated sequence of the HTT gene. This expansion generates a mutant huntingtin protein that contains an abnormally elongated polyglutamine tract, which, together with mutant transcript, causes cellular dysfunction. Currently, there is no curative treatment available to patients suffering from HD; however, the selective inhibition of the mutant allele expression is a promising therapeutic option. In this study, we developed a new class of CAG repeat-targeting silencing reagents that consist of self-duplexing CUG repeats. Self-duplex formation was induced through one or several U-base substitutions. A number of self-duplexing guide-strand-only short interfering RNAs have been tested through transfection into cells derived from HD patients, showing distinct activity profiles. The best reagents were highly discriminatory between the normal and mutant HTT alleles (allele selectivity) and the HTT transcript and other transcripts containing shorter CAG repeats (gene selectivity). We also demonstrated that the self-duplexing CUG repeat short interfering RNAs use the RNA interference pathway to elicit silencing, and repeat-targeting reagents showed similar activity and selectivity when expressed from short hairpin RNA vectors to achieve more durable silencing effects.<\/jats:p>","DOI":"10.1093\/nar\/gkt825","type":"journal-article","created":{"date-parts":[[2013,9,15]],"date-time":"2013-09-15T00:23:27Z","timestamp":1379204607000},"page":"10426-10437","source":"Crossref","is-referenced-by-count":34,"title":["Self-duplexing CUG repeats selectively inhibit mutant huntingtin expression"],"prefix":"10.1093","volume":"41","author":[{"given":"Agnieszka","family":"Fiszer","sequence":"first","affiliation":[{"name":"Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Olejniczak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Galka-Marciniak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Mykowska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wlodzimierz J.","family":"Krzyzosiak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,9,13]]},"reference":[{"key":"2024100208454696200_gkt825-B1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"2024100208454696200_gkt825-B2","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nature09267","article-title":"Mammalian microRNAs predominantly act to decrease target mRNA levels","volume":"466","author":"Guo","year":"2010","journal-title":"Nature"},{"key":"2024100208454696200_gkt825-B3","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/35078107","article-title":"Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells","volume":"411","author":"Elbashir","year":"2001","journal-title":"Nature"},{"key":"2024100208454696200_gkt825-B4","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1126\/science.1102513","article-title":"Argonaute2 is the catalytic engine of mammalian RNAi","volume":"305","author":"Liu","year":"2004","journal-title":"Science"},{"key":"2024100208454696200_gkt825-B5","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S0092-8674(02)00908-X","article-title":"Single-stranded antisense siRNAs guide target RNA cleavage in RNAi","volume":"110","author":"Martinez","year":"2002","journal-title":"Cell"},{"key":"2024100208454696200_gkt825-B6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrg2916","article-title":"Small RNA sorting: matchmaking for Argonautes","volume":"12","author":"Czech","year":"2011","journal-title":"Nat. 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