کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9200485 | 1581088 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Terminal antisense oligonucleotide modifications can enhance induced exon skipping
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب تکاملی
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چکیده انگلیسی
Induction of specific exon skipping during the processing of the dystrophin gene transcript is being pursued as a potential therapy for Duchenne muscular dystrophy. Antisense oligonucleotides directed at motifs involved in pre-mRNA processing can manipulate dystrophin exon incorporation in the mature gene transcript. We have compared the exon skipping ability of oligodeoxyribonucleotides with compounds of the identical sequence incorporating 2â²-O-methyl modified bases. Antisense oligonucleotides composed entirely of 2â²-O-methyl modified bases on a phosphorothioate backbone were consistently more efficient at inducing exon skipping than comparable oligodeoxyribonucleotides. Chimeric antisense oligonucleotides, mixtures of unmodified and 2â²-O-methyl modified bases, induced intermediate levels of exon skipping. In addition, we describe terminal modifications that may be incorporated into the 2â²-O-methyl antisense oligonucleotides to further enhance efficiency of exon skipping. Our findings suggest that 2â²-O-methyl antisense oligonucleotides should be considered for human clinical trials involving targeted exon skipping in dystrophin gene expression in preference to oligodeoxyribonucleotides.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuromuscular Disorders - Volume 15, Issues 9â10, October 2005, Pages 622-629
Journal: Neuromuscular Disorders - Volume 15, Issues 9â10, October 2005, Pages 622-629
نویسندگان
Bijanka L. Gebski, Stephen J. Errington, Russell D. Johnsen, Susan Fletcher, Stephen D. Wilton,