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Nucleic Acids Res. 2005 Jan 14;33(1):439-47. Print 2005.

Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality.

Author information

  • 1Center for Genomics and Bioinformatics, Karolinska Institutet 171 77 Stockholm, Sweden. joacim.elmen@cgb.ki.se

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.

PMID:
15653644
[PubMed - indexed for MEDLINE]
PMCID:
PMC546170
Free PMC Article

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