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

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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.
Publisher
OXFORD UNIV PRESS
Issue Date
2018-01
Language
English
Article Type
Article
Keywords

DOUBLE-STRANDED-RNA; IMMUNOGENIC CELL-DEATH; TOLL-LIKE RECEPTOR-3; STRUCTURAL BASIS; CANCER CELLS; PATTERN-RECOGNITION; VIRAL-RNA; VIRUS; ACTIVATION; INSIGHTS

Citation

NUCLEIC ACIDS RESEARCH, v.46, no.4, pp.1635 - 1647

ISSN
0305-1048
DOI
10.1093/nar/gky039
URI
http://hdl.handle.net/10203/240982
Appears in Collection
BS-Journal Papers(저널논문)CH-Journal Papers(저널논문)
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