Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy

RNA interference (RNAi) is the process of sequence-specific post-transcriptional gene silencing triggered by double-stranded RNAs 1 , 2 , 3 . In attempts to identify RNAi triggers that effectively function at lower concentrations, we found that synthetic RNA duplexes 25–30 nucleotides in length can...

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Bibliographic Details
Published in:Nature biotechnology 2005-02, Vol.23 (2), p.222-226
Main Authors: Kim, Dong-Ho, Behlke, Mark A, Rose, Scott D, Chang, Mi-Sook, Choi, Sangdun, Rossi, John J
Format: Article
Language:English
Subjects:
Agriculture
Bioinformatics
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - genetics
Gene Silencing - physiology
Gene Targeting - methods
Genetic Engineering - methods
Health. Pharmaceutical industry
Industrial applications and implications. Economical aspects
letter
Life Sciences
Miscellaneous
Ribonuclease III - chemistry
Ribonuclease III - metabolism
RNA, Small Interfering - chemistry
RNA, Small Interfering - genetics
Substrates
Transfection - methods
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Summary:RNA interference (RNAi) is the process of sequence-specific post-transcriptional gene silencing triggered by double-stranded RNAs 1 , 2 , 3 . In attempts to identify RNAi triggers that effectively function at lower concentrations, we found that synthetic RNA duplexes 25–30 nucleotides in length can be up to 100-fold more potent than corresponding conventional 21-mer small interfering RNAs (siRNAs). Some sites that are refractory to silencing by 21-mer siRNAs can be effectively targeted by 27-mer duplexes, with silencing lasting up to 10 d. Notably, the 27-mers do not induce interferon or activate protein kinase R (PKR). The enhanced potency of the longer duplexes is attributed to the fact that they are substrates of the Dicer endonuclease, directly linking the production of siRNAs to incorporation in the RNA-induced silencing complex. These results provide an alternative strategy for eliciting RNAi-mediated target cleavage using low concentrations of synthetic RNA as substrates for cellular Dicer-mediated cleavage.
ISSN:1087-0156
1546-1696
DOI:10.1038/nbt1051