한빛사논문
- 조회455
Daseuli Yu 2,6, Hee-Jeong Han 4,6, Jeonghye Yu 1,6, Jihye Kim 1,6, Gun-Hee Lee 4, Ju-Hee Yang 4, Byeong-Min Song 4, Dongseob Tark 4, Byeong-Sun Choi 5, Sang-Min Kang 4, Won Do Heo 1,3
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
2Life Science Research Institute, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
3KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
4Laboratory for Infectious Disease Prevention, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea
5Honam Regional Center for Disease Control and Prevention, RCDC, Korea Disease Control and Prevention Agency, Gwangju 61947, Republic of Korea
6These authors contributed equally
Corresponding authors: Sang-Min Kang, Won Do Heo
Abstract
CRISPR-Cas13-mediated viral genome targeting is a novel strategy for defending against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here, we generated mRNA-encoded Cas13b targeting the open reading frame 1b (ORF1b) region to effectively degrade the RNA-dependent RNA polymerase gene. Of the 12 designed CRISPR RNAs (crRNAs), those targeting the pseudoknot site upstream of ORF1b were found to be the most effective in suppressing SARS-CoV-2 propagation. Pseudoknot-targeting Cas13b reduced expression of the spike protein and attenuated viral replication by 99%. It also inhibited the replication of multiple SARS-CoV-2 variants, exhibiting broad potency. We validated the therapeutic efficacy of this system in SARS-CoV-2-infected hACE2 transgenic mice, demonstrating that crRNA treatment significantly reduced viral titers. Our findings suggest that the pseudoknot region is a strategic site for targeted genomic degradation of SARS-CoV-2. Hence, pseudoknot-targeting Cas13b could be a breakthrough therapy for overcoming infections by SARS-CoV-2 or other RNA viruses.
논문정보
- Research article
- 2023년 03월 (BRIC 등록일 2023-05-04)
- 국내 연구진
- 생명과학 > 세포생물학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
관련분야 논문보기
