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

作者：Lee Janghyun; Park Eun Byeol; Min Jiyoun; Sung 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

来源：Nucleic Acids Research, 2018, 46(4): 1635-1647.

DOI：10.1093/nar/gky039

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.

• 出版日期2018-2-28