The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Positional Effect of Chemical Modifications on Short Interference RNA Activity in Mammalian Cells
Abstract
A systematic study on the effect of 2'-sugar modifications (2'-F (2'-F-2'-deoxy-nucleoside residues), 2'-O-Me (2'-O-methyl-nucleoside residues), and 2'-O-MOE [2'-O-(2-methoxyethyl)]-nucleoside residues) in the antisense and sense strands of short interference RNA (siRNA) was performed in HeLa cells. The study of the antisense strand of siRNAs demonstrated that activity depends on the position of the modifications in the sequence. The siRNAs with modified ribonucleotides at the 5'-end of the antisense strand were less active relative to the 3'-modified ones. The 2'-F sugar was generally well-tolerated on the antisense strand, whereas the 2'-O-Me showed significant shift in activity depending on the position of modification. The 2'-O-MOE modification in the antisense strand resulted in less active siRNA constructs regardless of placement position in the construct. The incorporation of the modified residues, e.g., 2'-O-Me and 2'-O-MOE, in the sense strand of siRNA did not show a strong positional preference. These results may provide guidelines to design effective and stable siRNAs for RNA interference mediated therapeutic applications.
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Cites
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Cited by
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Self-citationThe chemical evolution of oligonucleotide therapies of clinical utility
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siRNA versus miRNA as therapeutics for gene silencing
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Metadata
- Authors
- Prakash, T. P., Allerson, C. R., Dande, P., Vickers, T. A., Sioufi, N., Jarres, R., Baker, B. F., Swayze, E. E., Griffey, R. H., & Bhat, B.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2005-05-27
- Volume
- 48
- Issue
- 13
- Pages
- 4247-4253
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2168993612
- Cited by
- 285
- References
- 53
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- closed
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- Prakash, T. P., Allerson, C. R., Dande, P., Vickers, T. A., Sioufi, N., Jarres, R., Baker, B. F., Swayze, E. E., Griffey, R. H., & Bhat, B. (2005). Positional Effect of Chemical Modifications on Short Interference RNA Activity in Mammalian Cells. Journal of Medicinal Chemistry. https://doi.org/10.1021/jm050044o
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