کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9921063 1559200 2005 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Central administration of small interfering RNAs in rats: A comparison with antisense oligonucleotides
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Central administration of small interfering RNAs in rats: A comparison with antisense oligonucleotides
چکیده انگلیسی
To date there are only few reports of the use of small interfering RNA (siRNA) in whole animals and most of these are restricted to systemic application of siRNAs targeting the liver. In our present studies we have investigated whether siRNAs can be used against a central target after intracerebroventricular (i.c.v.) application and compared their effects with those of antisense oligonucleotides. For this purpose we designed different siRNA and antisense oligonucleotide molecules against the rat hypothalamic melanocortin MC4 receptor and selected the siRNA and antisense oligonucleotide with the highest efficacy in vitro. We observed that siRNA, encompassing the same gene sequence as antisense oligonucleotides, induced a stronger inhibition of melanocortin MC4 receptor expression than antisense oligonucleotides. When fluorescence-labeled siRNA were applied i.c.v. in rats no label was detected in brain tissue in spite of the use of cell detergents to improve the delivery. In contrast to these findings the i.c.v. administered fluorescence-labeled antisense oligonucleotides reached the brain structures expressing melanocortin MC4 receptor and were taken up by the cells in these areas. In summary it seems as if 'naked' antisense oligonucleotides have an advantage over 'naked' siRNA for experiments in vivo. The development of optimized vector systems seems to be a prerequisite before siRNA can be regarded as a suitable experimental tool for in vivo studies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 522, Issues 1–3, 17 October 2005, Pages 30-37
نویسندگان
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