The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality
Open accessAbstract
Therapeutic application of the recently discovered small interfering RNA (siRNA) gene silencing phenomenon will be dependent on improvements in molecule bio-stability, specificity and delivery. To address these issues, we have systematically modified siRNA with the synthetic RNA-like high affinity nucleotide analogue, Locked Nucleic Acid (LNA). Here, we show that incorporation of LNA substantially enhances serum half-life of siRNA's, which is a key requirement for therapeutic use. Moreover, we provide evidence that LNA is compatible with the intracellular siRNA machinery and can be used to reduce undesired, sequence-related off-target effects. LNA-modified siRNAs targeting the emerging disease SARS, show improved efficiency over unmodified siRNA on certain RNA motifs. The results from this study emphasize LNA's promise in converting siRNA from a functional genomics technology to a therapeutic platform.
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Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
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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
A Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants
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Asymmetry in the Assembly of the RNAi Enzyme Complex
Schwarz, D. S., Hutvágner, G., Du, T., Xu, Z., Aronin, N., & Zamore, P. D. (2003) · Cell · doi:10.1016/s0092-8674(03)00759-1 · Cited by 2,922
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Functional siRNAs and miRNAs exhibit strand bias
Khvorova, A., Reynolds, A., & Jayasena, S. D. (2003) · Cell · doi:10.1016/s0092-8674(03)00801-8 · Cited by 2,645
Expression profiling reveals off-target gene regulation by RNAi
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Rational siRNA design for RNA interference
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Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate
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Cited by
Noncoding RNA therapeutics—Challenges and potential solutions
Winkle, M., El-Daly, S. M., Fabbri, M., & Calin, G. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00219-z · Cited by 1,551
siRNA versus miRNA as therapeutics for gene silencing
Lam, J. K. W., Chow, M. Y. T., Zhang, Y., & Leung, S. W. S. (2015) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2015.23 · Cited by 1,081
Progress towards in Vivo Use of siRNAs
Behlke, M. A. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.01.001 · Cited by 677
Bartlett, D. W. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj439 · Cited by 592
Chemical Modification of siRNAs for In Vivo Use
Behlke, M. A. (2008) · Oligonucleotides · doi:10.1089/oli.2008.0164 · Cited by 454
Metadata
- Authors
- Elm n, J.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-01-07
- Volume
- 33
- Issue
- 1
- Pages
- 439-447
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W1501059295
- Cited by
- 559
- References
- 30
- FWCI
- 13.02
- Type
- journal article
- Language
- en
- Open access
- gold
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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