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- W2127232012 abstract "The present study determines whether the expression of the huntingtin gene might be subject to antisense (AS)-mediated down-regulation. A series of AS oligodeoxynucleotides (ODNs) complementary to the huntingtin transcript [i.e., nucleotide (nt) -25 to 35] were designed and synthesized, and the AS efficacy was investigated by using a combination of in vitro transcription and translation to mimic in vivo conditions. An oligomer directed to nt -1 to 15 (ODN III) markedly reduced the incorporation of [(3)H]leucine into the huntingtin gene product in a dose-dependent manner (ED(50) of approximately 11.5 microM). ODNs that overlap with ODN III on both 5'- and 3'-flanking regions also produced translation arrest of the huntingtin protein; however, the AS-mediated effect of these ODNs represented approximately 50% of the effect of ODN III. In contrast, an ODN directed to nt 19 to 35 had no AS effect. The efficacy of ODN III also was investigated in an inducible, stably transfected PC-12 cell line expressing a truncated huntingtin exon 1 protein. In accordance with the cell free translation studies, ODN III (1-10 microM) markedly decreased the abundance of the huntingtin-green fluorescence fusion protein to 40 to 46% of the control levels. In summary, a series of putative AS candidates were screened for down-regulation of the huntingtin gene, and an ODN molecule directed to the methionine initiation codon was identified with maximum AS effects." @default.
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- W2127232012 date "2000-10-01" @default.
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- W2127232012 title "Antisense-mediated down-regulation of the human huntingtin gene." @default.
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