Systematic editing of synthetic RIG-I ligands to produce effective antiviral and anti-tumor RNA immunotherapies

Abstract Retinoic acid-inducible gene I (RIG-I) recognizes double-stranded viral RNAs (dsRNAs) containing two or three 5′ phosphates. A few reports of 5′-PPP-independent RIG-I agonists have emerged, but little is known about the molecular principles underlying their recognition. We recently found th...

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Bibliographic Details
Published in:Nucleic acids research 2018-02, Vol.46 (4), p.1635-1647
Main Authors: Lee, Janghyun, Park, Eun-Byeol, Min, Jiyoun, Sung, Si-Eun, Jang, Yejin, Shin, Jin Soo, Chun, Dongmin, Kim, Ki-Hun, Hwang, Jihyun, Lee, Mi-Kyung, Go, Yun Young, Kwon, Dohyeong, Kim, Meehyein, Kang, Suk-Jo, Choi, Byong-Seok
Format: Article
Language:English
Subjects:
Chemical Biology and Nucleic Acid Chemistry
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Summary:Abstract Retinoic acid-inducible gene I (RIG-I) recognizes double-stranded viral RNAs (dsRNAs) containing two or three 5′ phosphates. A few reports of 5′-PPP-independent RIG-I agonists have emerged, but little is known about the molecular principles underlying their recognition. We recently found that the bent duplex RNA from the influenza A panhandle promoter activates RIG-I even in the absence of a 5′-triphosphate moiety. Here, we report that non-canonical synthetic RNA oligonucleotides containing G-U wobble base pairs that form a bent helix can exert RIG-I-mediated antiviral and anti-tumor effects in a sequence- and site-dependent manner. We present synthetic RNAs that have been systematically modified to enhance their efficacy and we outline the basic principles for engineering RIG-I agonists applicable to immunotherapy.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gky039