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  Short antisense oligonucleotide-mediated inhibition is strongly dependent on oligo length and concentration but almost independent of location of the target sequence

Fakler, B., Herlitze, S., Amthor, B., Zenner, H., & Ruppersberg, J. P. (1994). Short antisense oligonucleotide-mediated inhibition is strongly dependent on oligo length and concentration but almost independent of location of the target sequence. The Journal of Biological Chemistry, 269(23), 16187-16194. Retrieved from http://www.jbc.org/cgi/content/abstract/269/23/16187?maxtoshow%3D%26HITS%3D10%26hits%3D10%26RESULTFORMAT%3D1%26author1%3Druppersberg%252C%2Bj%26searchid%3D1054379177270_599%26stored_search%3D%26FIRSTINDEX%3D0%26flag%3D%26sortspec%3Drelevance%26volume%3D269%26firstpage%3D16187.

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JBiolChem_269_1994_16187.pdf (Any fulltext), 2MB
 
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 Creators:
Fakler, Bernd1, Author              
Herlitze, Stefan2, Author              
Amthor , B., Author
Zenner, Hans−Peter, Author
Ruppersberg, J. Peter2, Author              
Affiliations:
1Max Planck Institute for Medical Research, Max Planck Society, ou_1125545              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

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 Abstract: The inhibitory effect of short antisense oligodeoxynucleotides (aODNs) on cRNA expression in Xenopus oocytes was measured using an electrophysiological assay based on subunit-specific block of cloned alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors. The effect of both phosphorothioate-modified (PS) and phosphodiester (PO) aODNs was strongly length dependent with a half-maximal inhibition calculated for an oligo length of 7.6 nucleotides (nt) and 9.9 nt, respectively. More than 95% inhibition was mediated by a PS aODN of 12 nt and by PO aODNs > or = 15 nt. At a given length PS and PO aODNs showed differential dependence of their inhibitory effect on the injected aODN concentration (half-maximal inhibition at 18 ng/microliter for a PO 12-mer and at 0.19 ng/microliter for a PS 12-mer) and differential saturation behavior. The inhibitory effect of aODNs, even as short as 8 nt for PS oligomers, was highly sequence specific, but almost independent of the position of the respective target site on the cRNA (for PS 8-mers, > or = 70% expression inhibition throughout the tested target sites from the translation initiation to the 3'-untranslated region). Thus, short PS aODNs can be reliably used in order to specifically inhibit protein expression in experiments addressing physiological, molecular biological, and perhaps even therapeutical issues.

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Language(s): eng - English
 Dates: 1994-01-261994-03-301994-06-10
 Publication Status: Published in print
 Pages: 8
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 Rev. Type: Peer
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Title: The Journal of Biological Chemistry
  Other : JBC
Source Genre: Journal
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Publ. Info: Baltimore, etc. : American Society for Biochemistry and Molecular Biology [etc.]
Pages: - Volume / Issue: 269 (23) Sequence Number: - Start / End Page: 16187 - 16194 Identifier: ISSN: 0021-9258
CoNE: https://pure.mpg.de/cone/journals/resource/954925410826_1