| Antisense effects of cholesterol-oligodeoxynucleotide conjugates associated with poly(alkylcyanoacrylate) nanoparticles. | |
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MedLine Citation:
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PMID: 7556188 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oligonucleotides covalently attached to a cholesteryl moiety are more stable in biological media and better taken up by eukaryotic cells. However, their anchoring in hydrophobic cellular membranes and endosomes after endocytosis restricts their access to cellular nucleic acids. New methods of cellular delivery and the biological activity of the conjugates were studied. The cholesteryl residue was conjugated via disulfide bond to the 5' or 3' terminal phosphate group of two oligodeoxyribonucleotide dodecamers complementary to the mutated region of Ha-ras oncogene mRNA. The conjugates were able to form complementary duplexes with the mutated 27-b target fragment of mRNA but not with the wild-type sequence. Efficient sequence-specific RNase H cleavage of complementary mRNA was induced with low (< or = 500 nM) concentrations of the conjugates. At higher concentrations, this cleavage was progressively inhibited, probably due to an interaction between RNase H and the cholesterol residue. The hydrophobic conjugates could be adsorbed onto poly(isohexylcyanoacrylate) nanoparticles via their cholesteryl moieties and delivered to eukaryotic cells. Cholesterol-conjugated oligonucleotides were able to sequence-specifically inhibit the proliferation of T24 human bladder carcinoma cells in culture. |
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Authors:
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G Godard; A S Boutorine; E Saison-Behmoaras; C Hélène |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of biochemistry / FEBS Volume: 232 ISSN: 0014-2956 ISO Abbreviation: Eur. J. Biochem. Publication Date: 1995 Sep |
Date Detail:
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Created Date: 1995-11-14 Completed Date: 1995-11-14 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0107600 Medline TA: Eur J Biochem Country: GERMANY |
Other Details:
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Languages: eng Pagination: 404-10 Citation Subset: IM |
Affiliation:
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Laboratoire de Biophysique, INSERM U201, CNRS URA481, Muséum National d'Histoire Naturelle, Paris, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adsorption Base Sequence Binding Sites Cholesterol / administration & dosage*, metabolism Cyanoacrylates Drug Delivery Systems Genes, ras Humans Molecular Sequence Data Oligonucleotides, Antisense / administration & dosage*, genetics, metabolism Particle Size Polymers RNA, Messenger / genetics, metabolism Ribonuclease H Tumor Cells, Cultured Vehicles |
| Chemical | |
Reg. No./Substance:
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0/Cyanoacrylates; 0/Oligonucleotides, Antisense; 0/Polymers; 0/RNA, Messenger; 0/Vehicles; 57-88-5/Cholesterol; EC 3.1.26.4/Ribonuclease H |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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