| Title | Programmable Synthetic Protein Circuits for the Identification and Suppression of Hepatocellular Carcinoma |
| Authors | Han, Xu Yang, Jiong Zeng, Fanhong Weng, Jun Zhang, Yue Peng, Qing Shen, Li Ding, Shigang Liu, Kaiyu Gao, Yi |
| Affiliation | Southern Med Univ, Zhujiang Hosp, Coinnovat Ctr Organ Failure Res, Dept Hepatobiliary Surg 2,State Key Lab Organ Fai, Guangzhou, Peoples R China Peking Univ, Hosp 3, Dept Gastroenterol, Beijing, Peoples R China Peking Univ, Sch Basic Med Sci, Dept Cell Biol, Hlth Sci Ctr, Beijing, Peoples R China |
| Keywords | RNA APTAMER GENE CIRCUITS T-CELLS INHIBITION EXPRESSION REGRESSION |
| Issue Date | 26-Jun-2020 |
| Publisher | MOLECULAR THERAPY-ONCOLYTICS |
| Abstract | Precisely identifying and killing tumor cells are diligent pursuits in oncotherapy. Synthesized gene circuits have emerged as an intelligent weapon to solve these problems. Gene circuits based on post-transcriptional regulation enable a faster response than systems based on transcriptional regulation, which requires transcription and translation, showing superior safety. In this study, synthetic-promoter-free gene circuits possessing two control layers were constructed to improve the specific recognition of tumor cells. Using split-TEV, we designed and verified the basic control layer of protein-protein interaction (PPI) sensing. Another orthogonal control layer was built to sense specific proteins. Two layers were integrated to generate gene circuits sensing both PPI and specific proteins, forming 10 logic gates. To demonstrate the utility of this system, the circuit was engineered to sense alpha-fetoprotein (AFP) expression and the PPI between YAP and 14-3-3 sigma, the matching profile of hepatocellular carcinoma (HCC). Gene-circuit-loaded cells distinguished HCC from other cells and released therapeutic antibodies, exhibiting in vitro and in vivo therapeutic effects. |
| URI | http://hdl.handle.net/20.500.11897/590200 |
| ISSN | 2372-7705 |
| DOI | 10.1016/j.omto.2020.03.008 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 基础医学院 |
