Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 439-447 |
| Number of pages | 9 |
| Journal | Nucleic Acids Research |
| Volume | 33 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 7 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
Cite this
Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. / Elmén, Joacim; Thonberg, Håkan; Ljungberg, Karl; Frieden, Miriam; Westergaard, Majken; Xu, Yunhe; Wahren, Britta; Liang, Zicai; Ørum, Henrik; Koch, Troels; Wahlestedt, Claes R.
In: Nucleic Acids Research, Vol. 33, No. 1, 07.03.2005, p. 439-447.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality
AU - Elmén, Joacim
AU - Thonberg, Håkan
AU - Ljungberg, Karl
AU - Frieden, Miriam
AU - Westergaard, Majken
AU - Xu, Yunhe
AU - Wahren, Britta
AU - Liang, Zicai
AU - Ørum, Henrik
AU - Koch, Troels
AU - Wahlestedt, Claes R
PY - 2005/3/7
Y1 - 2005/3/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=13744250159&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13744250159&partnerID=8YFLogxK
U2 - 10.1093/nar/gki193
DO - 10.1093/nar/gki193
M3 - Article
C2 - 15653644
AN - SCOPUS:13744250159
VL - 33
SP - 439
EP - 447
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 1
ER -