Engineering L7Ae for RNA-Only Delivery Kill Switch Targeting CMS2 Type Colorectal Cancer Cells
Engineering L7Ae for RNA-Only Delivery Kill Switch Targeting CMS2 Type Colorectal Cancer Cells
复制标题
工程化 L7Ae 用于仅 RNA 递送杀伤开关，靶向 CMS2 型结直肠癌细胞
DOI：
10.1021/acssynbio.0c00612
复制
发表时间：
2021
影响因子：
4.7
通讯作者：
Ding Shigang
中科院分区：
文献类型：
--
作者：
Yang Jiong;Ding Shigang
缺乏特异性靶向治疗来精确识别和杀死恶性细胞而不伤害其他细胞是结直肠癌（CRC）治疗的巨大挑战。在肿瘤的分子分类时代，CRC被分为四种共有分子亚型。占所有类型的37%，CMS 2组（典型类型）显示出显着特征：WNT和MYC信号激活。在这项研究中，我们设计了一种仅RNA递送的杀伤开关，以特异性消除CMS 2型CRC细胞。新设计的L7 Ae集传感和逻辑处理功能于一体，不仅可以检测β-catenin蛋白的稳定性和胞浆内Myc/Myc-nick的存在，还可以进行逻辑运算。该电路专门消除了HCT-116细胞，同时保留了其他类型的细胞，显示了精确靶向CMS 2型CRC的原理验证方法。
The lack of specific-targeting therapy to precisely identify and kill malignant cells while sparing others is a great challenge in colorectal cancer (CRC) treatment. In the era of molecular classification of tumors, CRC has been grouped into four Consensus Molecular Subtypes. Accounting for 37% of all types, the CMS2 group (canonical type) shows distinguishing features: WNT and MYC signaling activation. In this study, we designed an RNA-only delivery kill switch to specifically eliminate CMS2 type CRC cells. The sensing and logic processing functions are integrated by the newly engineered L7Ae, which can not only detect the stability of β-catenin protein and the presence of cytoplasm located Myc/Myc-nick, but also do logic computation. The circuit specifically eliminated HCT-116 cells while sparing other kinds of cells, showing a proof-of-principle approach to precisely target CMS2 type CRC.