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PMID: 15653644 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

Nucleic acids research ·Vol. 33 ·No. 1 ·2005-00-00 ·Pages 439-47

Elmén J, Thonberg H, Ljungberg K, Frieden M, Westergaard M, Xu Y, Wahren B, Liang Z, Ørum H, Koch T, Wahlestedt C

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.

MeSH Terms
Animals Cell Line Chlorocebus aethiops Humans Oligonucleotides Oligonucleotides, Antisense/chemistry PC12 Cells RNA Interference RNA Stability RNA, Small Interfering/blood,chemistry,pharmacology Rats Vero Cells
Chemicals
Oligonucleotides Oligonucleotides, Antisense RNA, Small Interfering locked nucleic acid
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Elmén Joacim
Center for Genomics and Bioinformatics, Karolinska Institutet 171 77 Stockholm, Sweden. [email protected]
Thonberg Håkan
Ljungberg Karl
Frieden Miriam
Westergaard Majken
Xu Yunhe
Wahren Britta
Liang Zicai
Ørum Henrik
Koch Troels
Wahlestedt Claes
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gki193
Email
[email protected]
Published
2005-00-00
Epub
2005-00-14
Pages
439-47
Language
English
Region
England
NLM ID
0411011
PMCID
PMC546170
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gki193 PMC Full Text View journal details
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