Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality
作者： J. Elm n
DOI: 10.1093/NAR/GKI193
关键词: Functional genomics 、 Cell biology 、 Molecular biology 、 RNA interference 、 Oligonucleotide 、 Locked nucleic acid 、 Small interfering RNA 、 RNA Stability 、 RNA 、 Biology 、 Gene silencing
摘要: 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 synthetic RNA-like high affinity nucleotide analogue, Locked Nucleic Acid (LNA). Here, show that incorporation LNA substantially enhances serum half-life siRNA's, which is a key requirement for therapeutic use. Moreover, provide evidence compatible intracellular machinery can used to reduce undesired, sequence-related off-target effects. LNA-modified siRNAs targeting emerging disease SARS, improved efficiency over unmodified certain motifs. The results from this study emphasize LNA's promise converting functional genomics technology platform.
oup.com
core.ac.uk
oxfordjournals.org
elsevier.com
paperity.org参考文章(31)
Sayda M. Elbashir, Jens Harborth, Winfried Lendeckel, Abdullah Yalcin, Klaus Weber, Thomas Tuschl, Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells Nature. ,vol. 411, pp. 494- 498 ,(2001) , 10.1038/35078107
Andrew Fire, SiQun Xu, Mary K. Montgomery, Steven A. Kostas, Samuel E. Driver, Craig C. Mello, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans Nature. ,vol. 391, pp. 806- 811 ,(1998) , 10.1038/35888
Sayda M Elbashir, Javier Martinez, Agnieszka Patkaniowska, Winfried Lendeckel, Thomas Tuschl, Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate The EMBO Journal. ,vol. 20, pp. 6877- 6888 ,(2001) , 10.1093/EMBOJ/20.23.6877
Frank Czauderna, Melanie Fechtner, Sibylle Dames, HuÈseyin AyguÈn, Anke Klippel, Gijsbertus J Pronk, Klaus Giese, JoÈrg Kaufmann, Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells Nucleic Acids Research. ,vol. 31, pp. 2705- 2716 ,(2003) , 10.1093/NAR/GKG393
Dwaine A. Braasch, Susan Jensen, Yinghui Liu, Kiran Kaur, Khalil Arar, Michael A. White, David R. Corey, RNA interference in mammalian cells by chemically-modified RNA Biochemistry. ,vol. 42, pp. 7967- 7975 ,(2003) , 10.1021/BI0343774
Rita Crinelli, Marzia Bianchi, Lucia Gentilini, Mauro Magnani, Design and characterization of decoy oligonucleotides containing locked nucleic acids. Nucleic Acids Research. ,vol. 30, pp. 2435- 2443 ,(2002) , 10.1093/NAR/30.11.2435
Yunhe Xu, Hong-Yan Zhang, Dorit Thormeyer, Ola Larsson, Quan Du, Joacim Elmén, Claes Wahlestedt, Zicai Liang, Effective small interfering RNAs and phosphorothioate antisense DNAs have different preferences for target sites in the luciferase mRNAs. Biochemical and Biophysical Research Communications. ,vol. 306, pp. 712- 717 ,(2003) , 10.1016/S0006-291X(03)01024-6
Aimee L Jackson, Steven R Bartz, Janell Schelter, Sumire V Kobayashi, Julja Burchard, Mao Mao, Bin Li, Guy Cavet, Peter S Linsley, Expression profiling reveals off-target gene regulation by RNAi Nature Biotechnology. ,vol. 21, pp. 635- 637 ,(2003) , 10.1038/NBT831
Ya-Lin Chiu, Tariq M. Rana, RNAi in Human Cells Molecular Cell. ,vol. 10, pp. 549- 561 ,(2002) , 10.1016/S1097-2765(02)00652-4
Jens Harborth, Sayda M. Elbashir, Kim Vandenburgh, Heiko Manninga, Stephen A. Scaringe, Klaus Weber, Thomas Tuschl, Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. Antisense & Nucleic Acid Drug Development. ,vol. 13, pp. 83- 105 ,(2003) , 10.1089/108729003321629638