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 R Wahlestedt

Research output: Contribution to journalArticle

409 Citations (Scopus)

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 languageEnglish
Pages (from-to)439-447
Number of pages9
JournalNucleic Acids Research
Volume33
Issue number1
DOIs
StatePublished - Mar 7 2005
Externally publishedYes

Fingerprint

RNA Stability
Small Interfering RNA
Nucleotide Motifs
Gene Silencing
Therapeutic Uses
Genomics
RNA Interference
Half-Life
locked nucleic acid
Nucleotides
RNA
Technology
Therapeutics
Serum

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 journalArticle

Elmén, J, Thonberg, H, Ljungberg, K, Frieden, M, Westergaard, M, Xu, Y, Wahren, B, Liang, Z, Ørum, H, Koch, T & Wahlestedt, CR 2005, 'Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality', Nucleic Acids Research, vol. 33, no. 1, pp. 439-447. https://doi.org/10.1093/nar/gki193
Elmén J, Thonberg H, Ljungberg K, Frieden M, Westergaard M, Xu Y et al. Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Research. 2005 Mar 7;33(1):439-447. https://doi.org/10.1093/nar/gki193
Elmén, Joacim ; Thonberg, Håkan ; Ljungberg, Karl ; Frieden, Miriam ; Westergaard, Majken ; Xu, Yunhe ; Wahren, Britta ; Liang, Zicai ; Ørum, Henrik ; Koch, Troels ; Wahlestedt, Claes R. / Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. In: Nucleic Acids Research. 2005 ; Vol. 33, No. 1. pp. 439-447.
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