Recent advances in bacterial therapeutics based on sense and response

Intelligent drug delivery is a promising strategy for cancer therapies. In recent years, with the rapid development of synthetic biology, some properties of bacteria, such as gene operability, excellent tumor colonization ability, and host-independent structure, make them ideal intelligent drug carriers and have attracted extensive attention. By implanting condition-responsive elements or gene circuits into bacteria, they can synthesize or release drugs by sensing stimuli. Therefore, compared with traditional drug delivery, the usage of bacteria for drug loading has better targeting ability and controllability, and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs. This review mainly introduces the development of bacterial-based drug delivery carriers, including mechanisms of bacterial targeting to tumor colonization, gene deletions or mutations, environment-responsive elements, and gene circuits. Meanwhile, we summarize the challenges and prospects faced by bacteria in clinical research, and hope to provide ideas for clinical translation.

Research progress of mammalian synthetic biology in biomedical field / 生物工程学报

Although still in its infant stage, synthetic biology has achieved remarkable development and progress during the past decade. Synthetic biology applies engineering principles to design and construct gene circuits uploaded into living cells or organisms to perform novel or improved functions, and it has been widely used in many fields. In this review, we describe the recent advances of mammalian synthetic biology for the treatment of diseases. We introduce common tools and design principles of synthetic gene circuits, and then we demonstrate open-loop gene circuits induced by different trigger molecules used in disease diagnosis and close-loop gene circuits used for biomedical applications. Finally, we discuss the perspectives and potential challenges of synthetic biology for clinical applications.

Smart therapeutics based on synthetic gene circuits / 生物工程学报

Synthetic biology has an important impact on biology research since its birth. Applying the thought and methods that reference from electrical engineering, synthetic biology uncovers many regulatory mechanisms of life systems, transforms and expands a series of biological components. Therefore, it brings a wide range of biomedical applications, including providing new ideas for disease diagnosis and treatment. This review describes the latest advances in the field of disease diagnosis and therapy based on mammalian cell or bacterial synthetic gene circuits, and provides new ideas for future smart therapy design.

Effect of irradiation-induced wt-p53 positive circuit on cell life cycle,apoptosis and irradiation sensitivity of lung adenocarcinoma cells / 第三军医大学学报

Objective To study the effects of irradiation-induced wt-p53 positive feedback circuit on cell life cycle,apoptosis rate and irradiation sensitivity of adenocarcinoma of lung in vitro.Methods The therapeutic group pE6R4-p53-EGFP/H1299 cells and the other 3 control groups H1299(p53-/-) ,pE6-p53EGFP/H1299 and pR4-p53-EGFP/H1299 cells were irradiated with 8-Mev electron beam generated by a linear accelerator at a dose rate of 400 cGy/min and a source-skin distance(SSD) of 100 cm,12 h exposure to irradiation.The cell life cycle and the rate of apoptosis were analyzed by FCM.Mean lethal dose(Do) and sensitive enhancement ratio(SER) index were calculated from the irradiation dose-survival curve.Results In 12 h post 4-Gy 8MV-X-ray irradiation,FCM analysis showed that most cells in therapeutic group were arrested at G0/G1 stage(75.13?1.42) %,compared with the 3 control groups(38.47?0.87) %,(62.57? 0.76) %and(51.23?2.41) %,respectively.After irradiation,the cell apoptotic rate in each group was higher than that in the cells without irradiation.The apoptotic rate in the therapeutic group was(23.73? 0.21) %,which was 5.69,1.51 and 2.57 folds respectively higher in the 3 control groups(4.17?0.12) %,(15.67?0.32) %and(9.23?0.15) %.Do values were 0.91,1.073 and 1.413 Gy respectively in pE6R4-p53-EGFP/H1299,pE6-p53-EGFP/H1299 and H1299 cells.The SER,derived from Do values,was 2.63 and 1.34,respectively.Conclusion Irradiation up-regulates wt-p53 gene expression,regulates cell cycle and induces cell apoptosis.Thus this positive feedback circuit increases the sensitivity of lung adenocarcinoma to irradiation.