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基于CRISPR-Cas9合成一种用于特异性杀死p53缺陷癌细胞的基因传感器。

Synthesizing a Genetic Sensor Based on CRISPR-Cas9 for Specifically Killing p53-Deficient Cancer Cells.

作者信息

Zhan Hengji, Xie Haibiao, Zhou Qun, Liu Yuchen, Huang Weiren

机构信息

Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Carson International Cancer Center , Shenzhen University School of Medicine , Shenzhen 518039 , China.

出版信息

ACS Synth Biol. 2018 Jul 20;7(7):1798-1807. doi: 10.1021/acssynbio.8b00202. Epub 2018 Jul 11.

Abstract

Cancer is still one of the greatest medical challenges in the world. The p53 protein plays an important role in the process of cancer formation. In addition, p53 is found as the most common mutant gene in cancers. Because of the central role of p53 in oncology, it is necessary to construct effective sensors to detect this protein. However, there are few methods to detect wild type p53 protein (WTP53) or to distinguish the wild type and mutant p53 proteins. In our study, we designed and constructed a p53 genetic sensor that detected the expression of WTP53 in cells. Moreover, we combined the p53 sensor with diphtheria toxin using the CRISPR-Cas9 system to construct a p53 genetic sensor that specifically killed p53-deficient cells such as tumor cells. Our study therefore developed a new way to treat cancers by using an available genetic sensor based on p53 protein.

摘要

癌症仍然是世界上最大的医学挑战之一。p53蛋白在癌症形成过程中起着重要作用。此外,p53是癌症中最常见的突变基因。由于p53在肿瘤学中的核心作用,构建有效的传感器来检测这种蛋白质是必要的。然而,检测野生型p53蛋白(WTP53)或区分野生型和突变型p53蛋白的方法很少。在我们的研究中,我们设计并构建了一种p53基因传感器,用于检测细胞中WTP53的表达。此外,我们使用CRISPR-Cas9系统将p53传感器与白喉毒素结合,构建了一种能特异性杀死p53缺陷细胞(如肿瘤细胞)的p53基因传感器。因此,我们的研究开发了一种基于p53蛋白的可用基因传感器来治疗癌症的新方法。

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