Letter abstract
Nature Biotechnology 26, 1379 - 1382 (2008)
Published online: 23 November 2008 | Corrected online: 9 February 2009 | doi:10.1038/nbt.1512
There is an Erratum (February 2009) associated with this Letter.
Asymmetric RNA duplexes mediate RNA interference in mammalian cells
Xiangao Sun1,3, Harry A Rogoff1,3 & Chiang J Li1,2
RNA interference (RNAi) has become an indispensable technology for biomedical research and has demonstrated the potential to become a new class of therapeutic1, 2, 3. Current RNAi technology in mammalian cells relies on short interfering RNA (siRNA) consisting of symmetrical duplexes of 19–21 base pairs (bp) with 3' overhangs4, 5. 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.
- Department of Therapeutic Biology, Boston Biomedical, Inc., 333 Providence Highway, Norwood, Massachusetts 02062, USA.
- Skip Ackerman Center for Molecular Therapeutics, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
- These authors contributed equally to this work.
Correspondence to: e-mail: cli@bostonbiomedical.com
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