Loading...

Table of Content

    30 April 2023, Volume 4 Issue 2
    Invited Review
    Applications of synthetic biology in disease diagnosis and treatment
    Xiaohao WU, Rongdong LIAO, Feiyun LI, Zhongtian OUYANG, Yi RAN, Weiyuan GONG, Minghao QU, Mingjue CHEN, Lijun LIN, Guozhi XIAO
    2023, 4(2):  244-262.  doi:10.12211/2096-8280.2022-059
    Asbtract ( 1635 )   HTML ( 169)   PDF (1515KB) ( 1531 )  
    Figures and Tables | References | Related Articles | Metrics

    Synthetic biology (SB) is an emerging discipline, which utilizes genetic engineering, systems biology, computer science, and other disciplines as tools to design, and even re-synthesize biological systems for specific needs. In the past 20 years, milestone breakthroughs in SB have been achieved and applied in the diagnosis and treatment of human diseases, particularly in the discovery of new drugs. SB not only provides new ideas and technical tools for the early and accurate diagnosis of diseases, but also develops a variety of new approaches for treating diseases, including cell therapy, bacteriotherapy, vaccines, and biomedical materials. Using SB-based methods, we can precisely diagnose diseases at an early stage, specifically engineer cells or bacteria, conduct mechanistic studies and drug screening, and rapidly produce vaccines and biomedical materials. SB with the "design-build-test" cycle greatly facilitates the development of new diagnostic and therapeutic approaches. Moreover, SB applies engineering principles (modularity, composability, abstraction, and standardization) to redefine biological systems in a more modular and composable way. Through this framework, the basic units of the biological system are fully characterized as standardized motifs (DNA sequences or gene-encoded products), and these motifs are mixed and matched to construct a fully functional genetic apparatus. By utilizing recently developed gene editing tools, such as the clustered regularly interspaced palindromic repeats (CRISPR/Cas9) technology, SB can integrate programmed devices into a chassis (e.g., bacteria and yeast), create new systems capable of producing target biomolecules or behaviors, and precisely manipulate the genome of cells and individuals to repair genetic defects. SB-based disease diagnosis and treatment will be one of the important development directions in the field of scientific research to completely change the way of diagnosis and clinical treatment of diseases in the future. This article reviews the applications of SB-based technologies in disease diagnosis and treatment, as well as in the production of vaccines and biomedical materials, as well as in new drug development.

    Applications of microbial synthetic biology in the diagnosis and treatment of diseases
    Xianyun GAO, Lingxue NIU, Ni JIAN, Ningzi GUAN
    2023, 4(2):  263-282.  doi:10.12211/2096-8280.2022-067
    Asbtract ( 1034 )   HTML ( 113)   PDF (2360KB) ( 930 )  
    Figures and Tables | References | Related Articles | Metrics

    Numerous bacteria and other microorganisms are living with the human body, which are parasitic in our skin, gastrointestinal tract, mouth, and other organs. While securing stable living environments, these microorganisms also help the human body to resist the invasion of pathogens, generate probiotic components (such as vitamins) and benefit the function of the immune system. Due to effective interactions between microorganisms and human being, the use of microbial agents to improve health status and treat diseases has become a research hotspot in recent years. For example, natural probiotics are used to regulate the intestinal microcommunity, and the bacterial community of healthy people is used to inoculate patients for the complementation of defective functions. Currently, the only FDA-approved and commercially available microbiotic-based treatment is fecal microbial transplantation for Clostridium difficile infections. Although fecal microbial transplantation has achieved some therapeutic effects, unclear mechanism underlying such a treatment and the uncontrollable operation process limit its applications. Therefore, there is an urgent need for better understanding of such a treatment to facilitate its application, and the development of synthetic biology has provided tools and methodology. Synthetic biology employs the ideas of modern molecular biotechnology and engineering principles to design, construct and optimize biological systems, and endow them with specific functions so that they can process information and synthesize target products including drugs. By developing gene circuits with specific functions in microorganisms, their metabolic pathways are intervened, even reconstructed, to sense physical and chemical signals and synthesize therapeutic products for use in smart and controllable treatment of diseases. Live biotherapeutic products (LBPs) have been proposed to prevent, diagnose and treat diseases by design and rebuilding of living organisms. In recent years, customized gene circuits have been continuously developed and introduced into microbial chassis cells to create engineered microorganisms with specific functions, providing a new scheme for disease treatment with recombinant LBPs. In this article, we summarize the latest progress of microbial synthetic biology in disease diagnosis and treatment, including inflammation, metabolic diseases, immune defects, pathogen infections, and cancers. Furthermore, challenges and further development are prospected. It has become a promising idea and method for clinical disease treatment with living microbial therapy by using living non-pathogenic engineered bacteria or probiotics equipped with smart gene circuits to sense and response to disease microenvironment for the controllable deliver of therapeutic agents.

    Merging the frontiers: synthetic biology for advanced bacteriophage design
    Qingli CHEN, Yigang TONG
    2023, 4(2):  283-300.  doi:10.12211/2096-8280.2022-070
    Asbtract ( 2033 )   HTML ( 139)   PDF (1602KB) ( 2102 )  
    Figures and Tables | References | Related Articles | Metrics

    Bacteriophages (phages), natural viruses known for infecting and killing bacteria, are the most diverse and abundant organisms on Earth. Within the past 100 years of research on phages, breakthroughs in genetics, molecular biology, and synthetic biology have been successfully achieved. The fascinating scientific history of phage therapy has been repeatedly reported, as drug-resistant bacteria are becoming increasingly prevalent. Although phages outnumber other species combined in nature (1031 in total), only a small fraction of them have been successfully exploited for fighting infections caused by drug-resistant bacteria. Therefore, there is an urgent need for implementing the motto of synthetic biology, "build to learn, build to use", and also using methods such as high-throughput sequencing and precise genome editing to create enhanced variants with unique features, improving efficacy and programmability for phage therapy. In the review, we discuss recent technological advances in phage genome engineering approaches and the potential applications of synthetic biology to engineer phages, such as modifying the host range of phages for practical needs, mining the extensive resources of phages in nature with the help of macro genomes, combining multi-omics technologies to reveal molecular mechanisms underlying phage-host interactions, regulating intestinal phages to maintain intestinal homeostasis for human health, and using big data and artificial intelligence to guide rational phage design. Synthetic biology is driving a paradigm shift in traditional experimental research by combining "Design-Build-Test-Learn (DBTL) cycles" to rational design for phages, making synthetically designed phages promising for both top-down system optimization and bottom-up life-form reconstruction.

    Potential application of synthetic biology in disease information recording and real-time monitoring
    Mengdan MA, Yuchen LIU
    2023, 4(2):  301-317.  doi:10.12211/2096-8280.2022-058
    Asbtract ( 723 )   HTML ( 70)   PDF (2573KB) ( 566 )  
    Figures and Tables | References | Related Articles | Metrics

    The ability to change information stored with genome in real time, efficiently, and dynamically is a major technological advance for in situ studies of cell biology and biology as well to control cell phenotype, and monitor disease progression. Since it was first used for mammalian gene editing, CRISPR-Cas technology has been widely used in research, medicine development and industrial production. In addition to indel mutations induced by Cas9 activity, recent advances in CRISPR-Cas have enabled DNA or RNA base to be edited more efficiently, and synthetic biologists are developing devices for information storage by harnessing the versatilities of CRISPR-Cas-based tools and gene circuits to engineer cells with modifications. DNA has a strong ability to store information that is stable for thousands of years. Key technology for monitoring cell signal change and behavior coordination is to use DNA as the recorder of molecular events in the body, which can transfer transient signals in cells into sustainable reactions, and store them permanently. With this key technology, researchers could get an in-depth understanding on transformation from genotype to phenotype in health and disease states, drug reactions with diseases in clinical trials for patients, and environmental changes associated with activities of human being. The goal of synthetic biology is to engineer cells with genetic circuits for new biological functions. CRISPR-Cas based tools are useful in developing genetic circuits because they can be easily repurposed by designing complementary gRNAs that interfere or act on any arbitrary nucleic acid sequence of interest. Although they are still in their infancy, CRISPR-Cas based tools are gaining popularity in encoding biological memory and tracing and forwarding genetic screening for each formed lineage. In this article, we summarize the progress and application of synthetic biology in DNA storage and real-time monitoring in cell, as well as the advantages of the CRISPR-Cas system processes and records of information in living cells. Finally, we highlight their prospects and challenges in research on diseases and treatments.

    Synthetic biology for next-generation genetic diagnostics
    Hailong LV, Jian WANG, Hao LV, Jin WANG, Yong XU, Dayong GU
    2023, 4(2):  318-332.  doi:10.12211/2096-8280.2022-061
    Asbtract ( 1120 )   HTML ( 73)   PDF (3022KB) ( 930 )  
    Figures and Tables | References | Related Articles | Metrics

    In recent years, rapid advances have been made for synthetic biology technologies, which contribute greatly to technological innovations and applications in genetic diagnostics. Diagnostic methods for accurate detection of diseases and monitoring treatment responses are essential for effective clinical managements. Synthetic biology seeks to redesign biological systems to perform new functions in a predictable manner. A review on recent advances in synthetic biology as a diagnostic method for accurate detection of diseases and monitoring therapeutic responses is essential for effective clinical management, and also important for prevention, prediction and prognosis of diseases. In this article, we first describes the categories of synthetic biology applications in genetic diagnostics, including different biosensors that have been developed for both in vitro and in vivo monitoring. Subsequently, perspectives of the next generation of genetic diagnostic technologies and progress of synthetic biology devices and technologies in genetic diagnostics are highlighted. In addition, we further address the current technical challenges in genetic diagnostics and clinical applications. Finally, we draw attention to the latest innovations in synthetic biology that may have a significant impact on the future applications of genetic diagnostics.

    Synthetic biology and viral vaccine development
    Zhaoling SHEN, Yanling WU, Tianlei YING
    2023, 4(2):  333-346.  doi:10.12211/2096-8280.2022-064
    Asbtract ( 1414 )   HTML ( 118)   PDF (1930KB) ( 904 )  
    Figures and Tables | References | Related Articles | Metrics

    Infectious diseases caused by viruses seriously endanger public health, and thus pose a great impact on socioeconomic development. Vaccine development is a critical and effective strategy for preventing the spread of infectious diseases to control them effectively. Generally, viral vaccines can be divided into various categories, such as whole virus vaccines (e.g. inactivated virus vaccines, split inactivated vaccines, and live attenuated vaccines), nucleic acid vaccines (DNA and RNA vaccines), recombinant subunits vaccines, and viral vector-based vaccines. However, strategies for developing viral vaccines still face some challenges, such as time-consuming, limited efficacy, and safety concern, which hinder their development, especially for fighting emerging infectious diseases timely. With the rapid development of synthetic biology, novel vaccines, named as synthetic vaccines, including genomic codon-optimized vaccines, nucleic acid vaccines, viral vector vaccines, virus-particle-like vaccines, and cell-based vaccines, have been designed, which can elicit immune protection more effectively. Synthetic biology technologies, such as codon optimization/deoptimization, genetically encoded click chemistry, and bioconjugation, can overcome weaknesses of traditional vaccines, and in the meantime facilitate the development of safe and efficient virus synthetic vaccines, which have been extensively explored. In this review, we summarize the current status of traditional vaccines, and also address the potential applications and advantages of synthetic biology technologies in the development of viral vaccines. At the end, we highlight the challenges of synthetic vaccines, which may provide insights and guidances for their design.

    Research progress in mosquito-borne flaviviruses transmission and the development of vaccines and drugs
    Xi YU, Jianying LIU, Gong CHENG
    2023, 4(2):  347-372.  doi:10.12211/2096-8280.2022-069
    Asbtract ( 845 )   HTML ( 55)   PDF (2078KB) ( 1158 )  
    Figures and Tables | References | Related Articles | Metrics

    Mosquito-borne viruses transmit between hosts and mosquito carriers through mosquito biting, which cause hundreds of millions of infections each year. These viral infections result in serious human diseases such as hemorrhagic fever, biphasic fever, arthritis, encephalitis and meningitis, which can lead to death if proper treatment is not available. Most mosquito-borne viruses are RNA viruses, with the flavivirus family as the most prevalent ones, including dengue virus, Zika virus, yellow fever virus, Japanese encephalitis virus and West Nile virus. Although there are effective vaccines for a few mosquito-borne flaviviruses, such as those for yellow fever virus and Japanese encephalitis virus, there are still no effective preventive vaccines and antiviral therapies for most mosquito-borne flaviviruses. Therefore, a comprehensive understanding of the mechanisms underlying the infection and transmission of mosquito-borne flaviviruses between vertebrate hosts and mosquitoes would provide insights for vaccine and drug development, enabling us to more effectively predict and control the transmission of mosquito-borne flavivirus and occurrence of the epidemics in the future, and providing solutions for addressing the public health threats posed by arboviruses. In this article, we firstly describe the biological and epidemiological characteristics of mosquito-borne flaviviruses, introduce the transmission routes and carrier models of mosquito-borne flaviviruses, and summarize the current research on the transmission and infection mechanisms of mosquito-borne flaviviruses between hosts and carriers. Furthermore, we highlight the development of novel vaccines and strategies for screening drugs to fight against mosquito-borne flaviviruses, providing an outlook for future research and development of vaccines and antiviral drugs.

    Synthetic biology and engineered T cell therapy
    Junhong XIE, Jingjing HE, Penghui ZHOU
    2023, 4(2):  373-393.  doi:10.12211/2096-8280.2022-063
    Asbtract ( 958 )   HTML ( 43)   PDF (2746KB) ( 695 )  
    Figures and Tables | References | Related Articles | Metrics

    In recent years, engineering T cell therapy has made great progress in tumor immunotherapy, which mainly includes T-cell receptor-engineered T cell (TCR-T) therapy and chimeric antigen receptor T cell (CAR-T) therapy. Due to their structure difference, TCR-T and CAR-T cells show different characteristics in signal activation and antigen recognition. CAR has scFv derived from antibody, containing CD3ζ and costimulatory domain(s), making engineered CAR able to recognize specific tumor associated antigens. Therefore, CAR has an ability to bind unprocessed tumor surface antigens without MHC processing, while TCR engages with both tumor intracellular and surface antigens embedded in MHC. While CAR-T cell therapy has demonstrated a significant clinical effect against malignant blood tumors, TCR-T cell therapies have been tested in hematological and solid tumors. Even though clinical results are encouraging for both approaches, several major challenges have been identified, including: target antigen selection such as less tumor toxicity and antigen escape, T cell homing to the tumor, T cell infiltration into the tumor, T cell persistence, and local immunosuppression in the tumor microenvironment. Synthetic biology technologies have enabled flexible reprogramming of engineered T cells to overcome the aforementioned limitations, bringing new opportunities for improving their safety and effectiveness, but the choice of a suitable target antigen is still a key for success. Moreover, improved preclinical TCR/CAR screening is likely to enhance the safety of engineered T cell therapies, and additional T cell engineering to further enhance engineered T cells at various levels has generated promising results, including: (1) modulation of affinity, (2) safety control elements, and (3) targeting TME components. Future developments will likely harness combinatorial strategies to overcome challenges posed by the tumors. In this article, we address structure and signal activation, target selection, affinity optimization, safety modification and gene editing strategies for engineered T cells, and also review the potential synthetic biological approaches and latest progress of engineered T cell therapy in the application of tumor immunotherapy.

    Progress in mammalian chromosome engineering
    Liyu ZHU, Yulong ZHAO, Wei LI, Libin WANG
    2023, 4(2):  394-406.  doi:10.12211/2096-8280.2022-072
    Asbtract ( 732 )   HTML ( 45)   PDF (1386KB) ( 667 )  
    Figures and Tables | References | Related Articles | Metrics

    Mammalian chromosome engineering refers to its editing through various methods to create animal models for chromosome diseases, pharmaceutical factories of human proteins, dissection of mechanism underlying evolution, and even synthetic life. In recent years, some milestone technologies of mammalian chromosome engineering, such as natural chromosome modifications, chromosome design and synthesis, and chromosome large fragment transfer, have been developed and integrated with each other. At the same time, embryonic stem cells have also been developed as a new chassis for mammalian synthetic biology. Applications of embryonic stem cells to synthetic biology greatly promote the development of mammalian chromosome engineering, giving birth to a large number of animal models for studies on diseases and evolution, including mouse models for Down syndrome, mice producing human monoclonal antibodies, and chromosome-ligation mice to study the biological effects of chromosome recombination. However, the manipulations of mammalian chromosomes are still challenging due to the lack of comprehensive understanding on chromosome composition and mammalian development. In addition to technological challenges, there are issues with bioethics and bio-safety. In this review, we review main technologies and current applications of mammalian chromosome engineering, and we also highlight future applications and challenges of mammalian chromosome engineering.

    Functions and applications of implantable brain-computer interfaces in medical treatment and scientific research
    Ling LIU, Shengjie ZHENG, Huixi DOU, Xiaojian LI
    2023, 4(2):  407-417.  doi:10.12211/2096-8280.2022-071
    Asbtract ( 793 )   HTML ( 36)   PDF (2259KB) ( 564 )  
    Figures and Tables | References | Related Articles | Metrics

    Brain-computer interfaces (BCI) currently exist primarily as a neuroprosthesis that allows electronic devices to communicate directly with parts of human brain, typically the cerebral cortex. In recent years, implantable BCI technology has made remarkable progress, and its applications have been expanded significantly, indicating that research achievements on neuroscience and their important transformation to BCI technology are interacted more efficiently and effectively. BCI is a process in which collected brain signals are decoded into digital information by a decoding algorithm through signal analysis, and computer, mechanical prosthesis, or other electrical stimulation device can be controlled based on this information. The most common applications of BCI are in medical applications, usually by capturing brain signals to synthesize understandable communications. For example, artificial tactile stimuli can be obtained through targeted electrical stimulation of the sensory cortex of brain, allowing patients with upper limb paralysis to imaginatively move their arms with the help from a tablet computer, restoring hand control through electrical stimulation of specific muscle tissues in the hand, and so on. Diseases like spinal cord injury, motor neuron disease, and stroke are currently untreatable, and BCI can be used to restore many interactive functions for paralyzed patients so that they can live and work normally, such as being able to communicate with others, such as talking, typing, and online socializing. On the other hand, BCI is also a powerful tool in neuroscience to study brain functions, such as conscious and subconscious feedback in brain-behavioral relationships. BCI for the motor function is the mainstream of research in these two fields. More and more BCI applications would be introduced in the near future, which could benefit paralyzed patients and patients with mental disorders, improving, even restoring their life qualities. In this article, we review the development of BCI and the different types of signal sources, with a focus on the medical-oriented and research-oriented BCI as well.