Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality
| Autor: | Henrik Ørum, Majken Westergaard, Yunhe Xu, Zicai Liang, Claes Wahlestedt, Joacim Elmén, Troels Koch, Miriam Frieden, Håkan Thonberg, Karl Ljungberg, Britta Wahren |
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| Rok vydání: | 2005 |
| Předmět: |
RNA Stability
Small interfering RNA Oligonucleotide Oligonucleotides RNA Oligonucleotides Antisense Biology PC12 Cells Molecular biology Article Cell Line Rats Cell biology RNA interference Chlorocebus aethiops Genetics Animals Humans Gene silencing RNA Interference RNA Small Interfering Locked nucleic acid Vero Cells Functional genomics |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| DOI: | 10.1093/nar/gki193 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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