| Photoinduced RNA interference using DMNPE-caged 2'-deoxy-2'-fluoro substituted nucleic acids in vitro and in vivo. | |
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MedLine Citation:
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PMID: 18414741 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Various chemical modifications to RNA have been incorporated in attempts to improve their pharmacological properties for RNAi interference (RNAi). Recent studies have shown that small interfering RNA (siRNA) containing 2'-fluoro modifications can elicit gene silencing through RNAi. Despite developments in using chemical modifications for increased stability, safety, and efficiency of these therapeutics, they still face challenges of spatial and temporal targeting. One potential targeting strategy is to use photocaging techniques, which involve the covalent attachment of photolabile compounds to the effector nucleic acid species that block bioactivity until exposed to near UV light. In this study we demonstrate that fully 2'-fluorinated nucleic acids (FNAs) can be caged for photoactivated gene silencing in cell culture and in zebrafish embryos. This strategy combines the improvement in chemical and enzymatic stability associated with 2'-substitutions with the targeting ability of a photoinducible trigger. Statistical alkylation of FNAs with 1-(4,5-dimethoxy-2-nitrophenyl)diazoethane (DMNPE) improved resistance to enzymatic degradation, reduced RNAi effectiveness, and protected the biological system from toxic doses of the effector. Photo-exposure to 365 nm light partially restored the silencing activity of the 2'-fluoro siRNAs. These results suggest that photocaging may offer control over RNAi therapeutics for spatially and temporally directed activation, while improving enzymatic stability and potentially enabling therapeutic dosing via light dose intensity. |
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Authors:
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Richard A Blidner; Kurt R Svoboda; Robert P Hammer; W Todd Monroe |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2008-03-31 |
Journal Detail:
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Title: Molecular bioSystems Volume: 4 ISSN: 1742-206X ISO Abbreviation: Mol Biosyst Publication Date: 2008 May |
Date Detail:
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Created Date: 2008-04-16 Completed Date: 2008-09-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101251620 Medline TA: Mol Biosyst Country: England |
Other Details:
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Languages: eng Pagination: 431-40 Citation Subset: IM |
Affiliation:
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Biological & Agricultural Engineering, Louisiana State University and LSU Agricultural Center, Baton Rouge, LA 70803, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Deoxyribonucleotides / pharmacology* Embryo, Nonmammalian / cytology, drug effects Fluorine* Gene Silencing / radiation effects Light* Nitrobenzenes / pharmacology* RNA Interference* / radiation effects Zebrafish |
| Chemical | |
Reg. No./Substance:
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0/Deoxyribonucleotides; 0/Nitrobenzenes; 154140-56-4/1-(4,5-dimethoxy-2-nitrophenyl)diazoethane; 7782-41-4/Fluorine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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