Precise tumor immune rewiring via synthetic CRISPRa circuits gated by concurrent gain/loss of transcription factors
Wang, Yafeng1,2; Zhang, Guiquan1; Meng, Qingzhou3; Huang, Shisheng4; Guo, Panpan2; Leng, Qibin3; Sun, Lingyun2; Liu, Geng1,5; Huang, Xingxu4,6; Liu, Jianghuai1,5
2022-03-18
发表期刊NATURE COMMUNICATIONS
EISSN2041-1723
卷号13期号:1
发表状态已发表
DOI10.1038/s41467-022-29120-y
摘要Reinvigoration of antitumor immunity has recently become the central theme for the development of cancer therapies. Nevertheless, the precise delivery of immunotherapeutic activities to the tumors remains challenging. Here, we explore a synthetic gene circuit-based strategy for specific tumor identification, and for subsequently engaging immune activation. By design, these circuits are assembled from two interactive modules, i.e., an oncogenic TF-driven CRISPRa effector, and a corresponding p53-inducible off-switch (NOT gate), which jointly execute an AND-NOT logic for accurate tumor targeting. In particular, two forms of the NOT gate are developed, via the use of an inhibitory sgRNA or an anti-CRISPR protein, with the second form showing a superior performance in gating CRISPRa by p53 loss. Functionally, the optimized AND-NOT logic circuit can empower a highly specific and effective tumor recognition/immune rewiring axis, leading to therapeutic effects in vivo. Taken together, our work presents an adaptable strategy for the development of precisely delivered immunotherapy.
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收录类别SCIE
语种英语
Scopus 记录号2-s2.0-85126708939
来源库Scopus
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/169257
专题生命科学与技术学院_博士生
生命科学与技术学院_PI研究组_黄行许组
通讯作者Liu, Geng; Huang, Xingxu; Liu, Jianghuai
作者单位1.State Key Laboratory of Pharmaceutical Biotechnology,Model Animal Research Center at Medical School of Nanjing University,Nanjing,210061,China
2.Department of Rheumatology and Immunology,The Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing,210008,China
3.Affiliated Cancer Hospital & Institute of Guangzhou Medical University,Guangzhou,78 Hengzhigang Road,510095,China
4.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China
5.Jiangsu Key Laboratory of Molecular Medicine,Medical School of Nanjing University,Nanjing,210093,China
6.Zhejiang Laboratory,Hangzhou,311100,China
通讯作者单位生命科学与技术学院
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Wang, Yafeng,Zhang, Guiquan,Meng, Qingzhou,et al. Precise tumor immune rewiring via synthetic CRISPRa circuits gated by concurrent gain/loss of transcription factors[J]. NATURE COMMUNICATIONS,2022,13(1).
APA Wang, Yafeng.,Zhang, Guiquan.,Meng, Qingzhou.,Huang, Shisheng.,Guo, Panpan.,...&Liu, Jianghuai.(2022).Precise tumor immune rewiring via synthetic CRISPRa circuits gated by concurrent gain/loss of transcription factors.NATURE COMMUNICATIONS,13(1).
MLA Wang, Yafeng,et al."Precise tumor immune rewiring via synthetic CRISPRa circuits gated by concurrent gain/loss of transcription factors".NATURE COMMUNICATIONS 13.1(2022).
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