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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 |
EISSN | 2041-1723 |
卷号 | 13期号:1 |
发表状态 | 已发表 |
DOI | 10.1038/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. |
URL | 查看原文 |
收录类别 | SCIE |
语种 | 英语 |
Scopus 记录号 | 2-s2.0-85126708939 |
来源库 | Scopus |
引用统计 | |
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 |
推荐引用方式 GB/T 7714 | 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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