Asymmetric RNA duplexes mediate RNA interference in mammalian cells

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Therapeutic Biology

Publication Date


Document Type



Life Sciences | Medicine and Health Sciences


RNA interference (RNAi) has become an indispensable technology for biomedical research and has demonstrated the potential to become a new class of therapeutic. Current RNAi technology in mammalian cells relies on short interfering RNA (siRNA) consisting of symmetrical duplexes of 19-21 base pairs (bp) with 3' overhangs. Here we report that asymmetric RNA duplexes with 3' and 5' antisense overhangs silence mammalian genes effectively. An asymmetric interfering RNA (aiRNA) of 15 bp was incorporated into the RNA-induced silencing complex (RISC) and mediated sequence-specific cleavage of the target mRNA between base 10 and 11 relative to the 5' end of the antisense strand. The gene silencing mediated by aiRNA was efficacious, durable and correlated with reduced off-target silencing by the sense strand. These results establish aiRNA as a scaffold structure for designing RNA duplexes to induce RNAi in mammalian cells.

DOI of Published Version



Nat Biotechnol. 2008 Dec;26(12):1379-82. Epub 2008 Nov 23. Link to article on publisher's site

Journal/Book/Conference Title

Nature biotechnology

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Link to Article in PubMed

PubMed ID