Background:Microfluidic systems have advantages such as a high throughput,small reaction volume,and precise control of the cellular position and environment.These advantages have allowed microfluidics to be widely use...Background:Microfluidic systems have advantages such as a high throughput,small reaction volume,and precise control of the cellular position and environment.These advantages have allowed microfluidics to be widely used in several fields of synthetic biology in recent years.Results'.In this article,we reviewed the microfluidic-based methods for synthetic biology from two aspects:the construction of synthetic gene circuits and the analysis of synthetic gene systems.We used some examples to illuminate the progresses and challenges in the steps of synthetic gene circuits construction and approaches of gene expression analysis with microfluidic systems.Conclusion:Comparing to traditional methods,microfluidic tools promise great advantages in the synthetic genetic circuit building and analysis process.Moreover,new microfluidic systems together with the mathematical modeling of synthetic circuits or consortiums are desirable to perform complex genetic circuit construction and understand the natural gene regulation in cells and population interactions better.展开更多
Background: Recently, optogenetics based on genetically encoded photosensitive proteins has emerged as an innovative technology platform to revolutionize manipulation of cellular behavior through fight stimulation. I...Background: Recently, optogenetics based on genetically encoded photosensitive proteins has emerged as an innovative technology platform to revolutionize manipulation of cellular behavior through fight stimulation. It has enabled user defined control of various cellular behaviors with spatiotemporal precision and minimal invasiveness, creating unprecedented opportunities for biomedical applications. Results: This article reviews current advances in optogenetic networks designed for the treatment of human diseases. We highlight the advantages of these optogenetic networks, as well as emerging questions and future perspectives. Conclusions: Various optogenetic systems have been engineered to control biological processes at all levels using light and applied for numerous diseases, such as metabolic disorders, cancer, and immune diseases. Continued development of optogenetic modules will be necessary to precisely control of gene expression magnitude towards clinical medical practice in the context of real-world problems.展开更多
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 ...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.展开更多
Synthetic biology provides a new paradigm for life science research(“build to learn”)and opens the future journey of biotechnology(“build to use”).Here,we discuss advances of various principles and technologies in...Synthetic biology provides a new paradigm for life science research(“build to learn”)and opens the future journey of biotechnology(“build to use”).Here,we discuss advances of various principles and technologies in the mainstream of the enabling technology of synthetic biology,including synthesis and assembly of a genome,DNA storage,gene editing,molecular evolution and de novo design of function proteins,cell and gene circuit engineering,cell-free synthetic biology,artificial intelligence(AI)-aided synthetic biology,as well as biofoundries.We also introduce the concept of quantitative synthetic biology,which is guiding synthetic biology towards increased accuracy and predictability or the real rational design.We conclude that synthetic biology will establish its disciplinary system with the iterative development of enabling technologies and the maturity of the core theory.展开更多
Bladder cancer(BC)is the most common malignant tumor of the genitourinary system.The age of individuals diagnosed with BC tends to decrease in recent years.A variety of standard therapeutic options are available for t...Bladder cancer(BC)is the most common malignant tumor of the genitourinary system.The age of individuals diagnosed with BC tends to decrease in recent years.A variety of standard therapeutic options are available for the clinical management of BC,but limitations exist.It is difficult to surgically eliminate small lesions,while radiation and chemotherapy damage normal tissues,leading to severe side effects.Therefore,new approaches are required to improve the efficacy and specificity of BC treatment.Synthetic biology is a field emerging in the last decade that refers to biological elements,devices,and materials that are artificially synthesized according to users’needs.In this review,we discuss how to utilize genetic elements to regulate BC-related gene expression periodically and quantitatively to inhibit the initiation and progression of BC.In addition,the design and construction of gene circuits to distinguish cancer cells from normal cells to kill the former but spare the latter are elaborated.Then,we introduce the development of genetically modified T cells for targeted attacks on BC.Finally,synthetic nanomaterials specializing in detecting and killing BC cells are detailed.This review aims to describe the innovative details of the clinical diagnosis and treatment of BC from the perspective of synthetic biology.展开更多
Mathematical modeling has become an increasingly important aspect of biological research. Computer simulations help to improve our understanding of complex systems by testing the validity of proposed mechanisms and ge...Mathematical modeling has become an increasingly important aspect of biological research. Computer simulations help to improve our understanding of complex systems by testing the validity of proposed mechanisms and generating experimentally testable hypotheses. However, significant overhead is generated by the creation, debugging, and perturbation of these computational models and their parameters, especially for researchers who are unfamiliar with programming or numerical methods. Dynetica 2.0 is a user-friendly dynamic network simulator designed to expedite this process. Models are created and visualized in an easy-to-use graphical interface, which displays all of the species and reactions involved in a graph layout. System inputs and outputs, indicators, and intermediate expressions may be incorporated into the model via the versatile "expression variable" entity. Models can also be modular, allowing for the quick construction of complex systems from simpler components. Dynetica 2.0 supports a number of deterministic and stochastic algorithms for performing time-course simulations. Additionally, Dynetica 2.0 provides built-in tools for performing sensitivity or dose response analysis for a number of different metrics. Its parameter searching tools can optimize specific objectives of the time course or dose response of the system. Systems can be translated from Dynetica 2.0 into MATLAB code or the Systems Biology Markup Language (SBML) format for further analysis or publication. Finally, since it is written in Java, Dynetica 2.0 is platform independent, allowing for easy sharing and collaboration between researchers.展开更多
A central goal of synthetic biology is to apply successful principles that have been developed in electronic and chemical engineering to construct basic biological functional modules, and through rational design, to b...A central goal of synthetic biology is to apply successful principles that have been developed in electronic and chemical engineering to construct basic biological functional modules, and through rational design, to build synthetic biological systems with predetermined functions. Here, we apply the reverse engineering design principle of biological networks to synthesize a gene circuit that executes semi-log dose-response, a logarithmically linear sensing function, in Escherichia coil cells. We first mathematically define the object function semi-log dose-response, and then search for tri-node network topologies that can most robustly execute the object function. The simplest topology, transcriptional coherent feed-forward loop (TCFL), among the searching results is mathematically analyzed; we find that, in TCFL topology, the semi-log dose-response function arises from the additive effect of logarithmical linearity intervals of Hill functions. TCFL is then genetically implemented in E. coil as a logarithmically linear sensing biosensor for heavy metal ions [mercury (II)]. Functional characterization shows that this rationally designed biosensor circuit works as expected. Through this study we demonstrated the potential application of biological network reverse engineering to broaden the computational power of synthetic biology.展开更多
基金This study was supported the National Key Research and Development Project(SQ2018YFA090070-03 and 2020YFA0906900)the National Natural Science Foundation of China(Nos.11974002 and 11674010).
文摘Background:Microfluidic systems have advantages such as a high throughput,small reaction volume,and precise control of the cellular position and environment.These advantages have allowed microfluidics to be widely used in several fields of synthetic biology in recent years.Results'.In this article,we reviewed the microfluidic-based methods for synthetic biology from two aspects:the construction of synthetic gene circuits and the analysis of synthetic gene systems.We used some examples to illuminate the progresses and challenges in the steps of synthetic gene circuits construction and approaches of gene expression analysis with microfluidic systems.Conclusion:Comparing to traditional methods,microfluidic tools promise great advantages in the synthetic genetic circuit building and analysis process.Moreover,new microfluidic systems together with the mathematical modeling of synthetic circuits or consortiums are desirable to perform complex genetic circuit construction and understand the natural gene regulation in cells and population interactions better.
文摘Background: Recently, optogenetics based on genetically encoded photosensitive proteins has emerged as an innovative technology platform to revolutionize manipulation of cellular behavior through fight stimulation. It has enabled user defined control of various cellular behaviors with spatiotemporal precision and minimal invasiveness, creating unprecedented opportunities for biomedical applications. Results: This article reviews current advances in optogenetic networks designed for the treatment of human diseases. We highlight the advantages of these optogenetic networks, as well as emerging questions and future perspectives. Conclusions: Various optogenetic systems have been engineered to control biological processes at all levels using light and applied for numerous diseases, such as metabolic disorders, cancer, and immune diseases. Continued development of optogenetic modules will be necessary to precisely control of gene expression magnitude towards clinical medical practice in the context of real-world problems.
基金supported by National Natural Science Foundation of China(Nos.32171372 and 31872755)Jiangsu Outstanding Youth Funding(BK20190007,China)Logistics research projects(BWS20J017,China).
文摘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.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29050100,XDB29050500,XDA24020102)to X.E.Zhang,C.Liu and C.Gao,respectivelythe National Natural Science Foundation of China(31725002,31861143017,32022044,62050152 and 32071428)to J.Dai,Y.Yuan,C.You,and X.Wang,respectivelythe National Key Research and Development Program of China(2020YFA0907700,2018YFA0901600,2019YFA09004500)to Y.Feng and P.Wei。
文摘Synthetic biology provides a new paradigm for life science research(“build to learn”)and opens the future journey of biotechnology(“build to use”).Here,we discuss advances of various principles and technologies in the mainstream of the enabling technology of synthetic biology,including synthesis and assembly of a genome,DNA storage,gene editing,molecular evolution and de novo design of function proteins,cell and gene circuit engineering,cell-free synthetic biology,artificial intelligence(AI)-aided synthetic biology,as well as biofoundries.We also introduce the concept of quantitative synthetic biology,which is guiding synthetic biology towards increased accuracy and predictability or the real rational design.We conclude that synthetic biology will establish its disciplinary system with the iterative development of enabling technologies and the maturity of the core theory.
基金supported by the National Key R&D Program of China(2019YFA0906003)the National Natural Science Foundation of China(32000989)+5 种基金China Postdoctoral Science Foundation Grant(2020M682911 and 2020M670051ZX)Guangdong Special Support Program(2021JC06Y578)the Shenzhen Municipal Government of China(JCYJ20200109120016553,CJGJZD20200617102403009,and RCBS20210706092256081)the Sanming Project of Shenzhen Health and Family Planning Commission(SZSM202011017)Shenzhen Institute of Synthetic Biology Scientific Research Program(ZTXM20214005)the Shenzhen High-level Hospital Construction Fund。
基金supported by the National Key Research and Development Program of China(No.2018YFA0902802).
文摘Bladder cancer(BC)is the most common malignant tumor of the genitourinary system.The age of individuals diagnosed with BC tends to decrease in recent years.A variety of standard therapeutic options are available for the clinical management of BC,but limitations exist.It is difficult to surgically eliminate small lesions,while radiation and chemotherapy damage normal tissues,leading to severe side effects.Therefore,new approaches are required to improve the efficacy and specificity of BC treatment.Synthetic biology is a field emerging in the last decade that refers to biological elements,devices,and materials that are artificially synthesized according to users’needs.In this review,we discuss how to utilize genetic elements to regulate BC-related gene expression periodically and quantitatively to inhibit the initiation and progression of BC.In addition,the design and construction of gene circuits to distinguish cancer cells from normal cells to kill the former but spare the latter are elaborated.Then,we introduce the development of genetically modified T cells for targeted attacks on BC.Finally,synthetic nanomaterials specializing in detecting and killing BC cells are detailed.This review aims to describe the innovative details of the clinical diagnosis and treatment of BC from the perspective of synthetic biology.
文摘Mathematical modeling has become an increasingly important aspect of biological research. Computer simulations help to improve our understanding of complex systems by testing the validity of proposed mechanisms and generating experimentally testable hypotheses. However, significant overhead is generated by the creation, debugging, and perturbation of these computational models and their parameters, especially for researchers who are unfamiliar with programming or numerical methods. Dynetica 2.0 is a user-friendly dynamic network simulator designed to expedite this process. Models are created and visualized in an easy-to-use graphical interface, which displays all of the species and reactions involved in a graph layout. System inputs and outputs, indicators, and intermediate expressions may be incorporated into the model via the versatile "expression variable" entity. Models can also be modular, allowing for the quick construction of complex systems from simpler components. Dynetica 2.0 supports a number of deterministic and stochastic algorithms for performing time-course simulations. Additionally, Dynetica 2.0 provides built-in tools for performing sensitivity or dose response analysis for a number of different metrics. Its parameter searching tools can optimize specific objectives of the time course or dose response of the system. Systems can be translated from Dynetica 2.0 into MATLAB code or the Systems Biology Markup Language (SBML) format for further analysis or publication. Finally, since it is written in Java, Dynetica 2.0 is platform independent, allowing for easy sharing and collaboration between researchers.
基金This work is part of the project for the 2010 team of Peking University in the international genetically engineered machine (iGEM) competition. H. Zhang. designed the project, performed the experiments and modeling simulation, and wrote the manuscript. Y. Sheng., A. Liu, and Q. Wu performed the experiments. Y. Lu and Z. Yin performed the modeling simulation. Y. Cao and W. Zeng performed the modeling simulation and wrote the manu- script. Q. Ouyang designed the project and wrote the manuscript. We would like to thank F. Hao, X. He, W. Wei, C. Xu, and L. Ji for their technical assistance the BioBrick Foundation for providing DNA materials and Anne O. Summers for supplying the plasmid carrying MerR gene. We thank Peking University for its financial support. This work is also partially supported by the National Nature Science Foundation of China (Nos. 10721463, 110740 09), the National Basic Research Program of China (Nos. 2009CB918500, 2012AA02A702), and the National Science Fund for Talent Training in Basic Science of China (Nos. J1030310, J1103205).
文摘A central goal of synthetic biology is to apply successful principles that have been developed in electronic and chemical engineering to construct basic biological functional modules, and through rational design, to build synthetic biological systems with predetermined functions. Here, we apply the reverse engineering design principle of biological networks to synthesize a gene circuit that executes semi-log dose-response, a logarithmically linear sensing function, in Escherichia coil cells. We first mathematically define the object function semi-log dose-response, and then search for tri-node network topologies that can most robustly execute the object function. The simplest topology, transcriptional coherent feed-forward loop (TCFL), among the searching results is mathematically analyzed; we find that, in TCFL topology, the semi-log dose-response function arises from the additive effect of logarithmical linearity intervals of Hill functions. TCFL is then genetically implemented in E. coil as a logarithmically linear sensing biosensor for heavy metal ions [mercury (II)]. Functional characterization shows that this rationally designed biosensor circuit works as expected. Through this study we demonstrated the potential application of biological network reverse engineering to broaden the computational power of synthetic biology.