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

Joacim Elmén, Håkan Thonberg, Karl Ljungberg, Miriam Frieden, Majken Westergaard, Yunhe Xu, Britta Wahren, Zicai Liang, Henrik Ørum, Troels Koch, Claes Wahlestedt

Research output: Contribution to journalArticlepeer-review

442 Scopus citations


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 languageEnglish (US)
Pages (from-to)439-447
Number of pages9
JournalNucleic acids research
Issue number1
StatePublished - 2005
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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