Central administration of small interfering RNAs in rats : a comparison with antisense oligonucleotides

Senn, C. and Hangartner, C. and Moes, S. and Guerini, D. and Hofbauer, K. G.. (2005) Central administration of small interfering RNAs in rats : a comparison with antisense oligonucleotides. European Journal of Pharmacology, Vol. 522, H. 1-3. pp. 30-37.

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Official URL: http://edoc.unibas.ch/dok/A5258614

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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 MC(4) 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 MC(4) 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 MC(4) 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Pharmacology/Neurobiology (Hofbauer)
UniBasel Contributors:Hofbauer, Karl G.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier Biomedical Press
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:20
Deposited On:22 Mar 2012 13:20

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