The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells
Open accessAbstract
Double-stranded short interfering RNAs (siRNA) induce post-transcriptional silencing in a variety of biological systems. In the present study we have investigated the structural requirements of chemically synthesised siRNAs to mediate efficient gene silencing in mammalian cells. In contrast to studies with Drosophila extracts, we found that synthetic, double-stranded siRNAs without specific nucleotide overhangs are highly efficient in gene silencing. Blocking of the 5'-hydroxyl terminus of the antisense strand leads to a dramatic loss of RNA interference activity, whereas blocking of the 3' terminus or blocking of the termini of the sense strand had no negative effect. We further demonstrate that synthetic siRNA molecules with internal 2'-O-methyl modification, but not molecules with terminal modifications, are protected against serum-derived nucleases. Finally, we analysed different sets of siRNA molecules with various 2'-O-methyl modifications for stability and activity. We demonstrate that 2'-O-methyl modifications at specific positions in the molecule improve stability of siRNAs in serum and are tolerated without significant loss of RNA interference activity. These second generation siRNAs will be better suited for potential therapeutic application of synthetic siRNAs in vivo.
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Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
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Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456
Role for a bidentate ribonuclease in the initiation step of RNA interference
Bernstein, E., Caudy, A. A., Hammond, S. M., & Hannon, G. J. (2001) · Nature · doi:10.1038/35053110 · Cited by 4,892
Hannon, G. J. (2002) · Nature · doi:10.1038/418244a · Cited by 3,538
RNA interference is mediated by 21- and 22-nucleotide RNAs
Elbashir, S. M., Lendeckel, W., & Tuschl, T. (2001) · Genes & Development · doi:10.1101/gad.862301 · Cited by 3,310
An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells
Hammond, S. M., Bernstein, E., Beach, D., & Hannon, G. J. (2000) · Nature · doi:10.1038/35005107 · Cited by 3,003
Regulation of Heterochromatic Silencing and Histone H3 Lysine-9 Methylation by RNAi
Volpe, T. A., Kidner, C., Hall, I. M., Teng, G., Grewal, S. I. S., & Martienssen, R. A. (2002) · Science · doi:10.1126/science.1074973 · Cited by 2,055
Argonaute2, a Link Between Genetic and Biochemical Analyses of RNAi
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Single-Stranded Antisense siRNAs Guide Target RNA Cleavage in RNAi
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Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate
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The chemical evolution of oligonucleotide therapies of clinical utility
Khvorova, A., & Watts, J. K. (2017) · Nature Biotechnology · doi:10.1038/nbt.3765 · Cited by 1,216
Strategies for silencing human disease using RNA interference
Kim, D. H., & Rossi, J. J. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2006 · Cited by 1,078
Illuminating the silence: understanding the structure and function of small RNAs
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Metadata
- Authors
- Czauderna, F.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-06-01
- Volume
- 31
- Issue
- 11
- Pages
- 2705-2716
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W1984085632
- Cited by
- 623
- References
- 28
- FWCI
- 9.76
- Type
- journal article
- Language
- en
- Open access
- bronze
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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