کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10770752 | 1050835 | 2005 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sleeping Beauty-mediated down-regulation of huntingtin expression by RNA interference
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کلمات کلیدی
Sleeping Beauty transposonRNA interference - RNA تداخل کنندهSmall interfering RNA - RNA تداخل کوچکNonviral gene transfer - انتقال ژن غیر ویروسیHuntington disease - بیماری هانتینگتونpost-transcriptional gene silencing - خاموش کردن ژن post-transcriptionalPolyglutamine - پلیگلوتامینNeuronal cell culture - کشت سلولی عصبی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Huntington disease (HD) is a devastating neurologic disorder that is characterized by abnormal expansion of a CAG nt repeat in the first exon of the huntingtin (htt) gene, producing a mutant protein with an elongated polyglutamine stretch. The presence of this mutant protein is correlated with the characteristic loss of striatal neurons and the clinical manifestation of HD. Currently there is no effective treatment for the associated cell death. The aim of this study was to evaluate an innovative strategy combining RNA interference (RNAi) and gene transfer via the nonviral Sleeping Beauty (SB) transposon system to down-regulate Htt expression. siRNA expression vectors were designed to target exons 1, 4, 6, and 62 of the human htt gene. Real-time RT-PCR and Western blot analysis were used to quantify Htt mRNA and protein levels, respectively, in human cell lines. The results indicated that selected siRNA constructs significantly decreased Htt mRNA and protein levels relative to controls. In addition, SB transposition of the siRNA constructs into the genome reduced long-term protein expression of Htt by â¼90%. The combination of siRNA, the SB transposon, and an accurate transgenic mouse model may permit evaluation of this approach in preventing the pathogenesis associated with expression of mutant Htt.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 329, Issue 2, 8 April 2005, Pages 646-652
Journal: Biochemical and Biophysical Research Communications - Volume 329, Issue 2, 8 April 2005, Pages 646-652
نویسندگان
Zongyu J. Chen, Betsy T. Kren, Phillip Y.-P. Wong, Walter C. Low, Clifford J. Steer,