2021, 10(4):3-16. DOI: 10.12146/j.issn.2095-3135.20210510002
Abstract:Synthetic biology is an emerging and popular engineering science in the field of life sciences.Its essence is to rationally design, transform and even resynthesize biological systems according to specific goals under the guidance of engineering thoughts, and to study the life sciences focusing on basic problems or major challenges of human beings by constructing artificial biological systems. The core of synthetic biology is to understand the essence of life (build to learn) and creating social and economic value (build to use) through research. Synthetic biotechnology has been evaluated by many countries as one of the disruptive technologies in the future. With broad application prospects in the biomedical field, synthetic biology has become a disruptive science and technology field that developed countries such as Europe and the United States are striving to develop. Based on bibliometrics and patent analysis of synthetic biomedicine, synthetic biomedicine-related literature and patents have shown explosive growth since 2014. The development of synthetic biomedicine in the United States has first-mover advantages, outstanding achievements, while China with outstanding strength is catching up with and surpassing by degrees. This article analyzes the development trend of synthetic biomedicine applications in order to provide a reference for the development and layout of synthetic biomedicine in China.
2021, 10(4):17-32. DOI: 10.12146/j.issn.2095-3135.20210427014
Abstract:The development of bacterial resistance to antimicrobial drugs is a major challenge in the clinical treatment of infectious diseases and has received widespread attention. Bacteria acquire resistance through a variety of mechanisms to evade killing by antimicrobial drugs. Phage is a generic term for bacteriophage that infects microorganisms such as bacteria, fungi, actinomycetes or spirochetes. Its application in the treatment of infectious diseases with drug-resistant bacteria in clinical settings has achieved some success in recent years, but the ensuing problem of phage resistance has limited its application. This paper reviews the main mechanisms of bacterial drug resistance and phage resistance, and the main current advances in synthetic biology in addressing bacterial resistance to antibiotics and resistance to natural phages.
2021, 10(4):33-49. DOI: 10.12146/j.issn.2095-3135.20210427012
Abstract:To gain the desirable activity of biomolecules, directed evolution is served as a competent technology depending on high quality mutant library, effective selection and screening, which has been widely used in food, industry and medical fields. CRISPR (clustered regularly interspaced short palindromic repeats) has developed rapidly in recent years, and various CRISPR derivatives have been developed to meet directed evolution, allowing people to evolve specific genes in situ in a wide range of hosts. At the same time, the way of generating genetic diversity through artificial or natural pathways has given people more choices, and more efficient evolution strategies can be adopted according to research needs. This article will first introduce the CRISPR tools, then summarize the CRISPR-mediated mutation and screening platforms and finally discuss the development trends and opportunities of the CRISPR in the field of directed evolution.
2021, 10(4):50-66. DOI: 10.12146/j.issn.2095-3135.20210427010
Abstract:Pseudomonas aeruginosa has strong intrinsic antibiotic drug resistance and the ability to acquire further resistance mechanisms to multiple antibiotics. Therefore, for patients with Pseudomonas aeruginosa infection, the emergence of multidrug-resistant Pseudomonas aeruginosa often means that the efficacy of antibiotics has deteriorated or even completely ineffective. The development of new antibiotics takes a long time and is costly. Therefore, looking for new antibacterial drugs to replace antibiotics, finding new drug carriers, and new treatment methods to increase the activity of antibacterial drugs against multidrug resistant Pseudomonas aeruginosa infection treatment is of great significance. In this paper, some basic laboratory and clinical studies about using organic acids, antimicrobial peptides, nanoparticles, bacteriophages, hydrogels, bacterias in the treatment of Pseudomonas aeruginosa infection were reviewed and summarized to provide a reference for the treatment of multi-antibiotics resistant Pseudomonas aeruginosa infection.
2021, 10(4):67-77. DOI: 10.12146/j.issn.2095-3135.20210427003
Abstract:Epstein-Barr virus causes a ubiquitous infection in adults worldwide. It is also a oncogenic virus that is associated with many cancers, including nasopharyngeal carcinoma which is one of the predominant tumor in South China. However, so far, a vaccine against Epstein-Barr virus was not yet available in the world and there is no effective immunotherapy against those Epstein-Barr virus associated carcinomas. With the advantages of high stability, biocompatibility, low toxicity and multifunctional regions, the nextgeneration nanoparticles has been successfully applied in the research of Epstein-Barr virus vaccines. In this article, the recent advances of nanoparticles, including exosomes, virus-like particles, self-assembling ferritin nanoparticles and other nanoparticles using for prevention and against of Epstein-Barr virus infections have been reviewed and further discussed. Finally, the opportunities and challenges faced by engineered nanoparticles in the clinical application are prospected.
2021, 10(4):78-92. DOI: 10.12146/j.issn.2095-3135.20210427011
Abstract:Bacteriotherapy is one of the important direction in the field of cancer therapy. The increasing development of synthetic biology provides more diversified, more effective and safer therapeutic strategies for bacterial anti-cancer therapy. In this review, the excellent clinical examples in the field of bacterial anti-cancer therapy are summarized, the current research progress and bottleneck problems are introduced in detail. The application of synthetic biology in promoting the clinical development of live bacterial therapeutics is also discussed. Moreover, the important role and the future development trend of synthetic biology are prospected in view of the effectiveness and biosafety of clinical live bacterial therapeutics.
2021, 10(4):93-101. DOI: 10.12146/j.issn.2095-3135.20210427004
Abstract:The efficacy of current anti-tumor therapies has suffered from possible side effects and the poor accessibility of drugs to the tumor core. Although a variety of bacteria in nature have the potential to be used as anti-tumor drugs, lacking controllability and potential safety issues have limited their usage in tumor treatment. With the development of synthetic biology, bacteria are extensively programmed under engineering disciplines to possess less toxicity and enhanced ability to target tumors, sense the lesions and locate the lesions accurately. Applying engineered bacteria as vectors to directly carry drugs or express and release molecular therapeutics has greatly improved the efficacy of the tumor treatment. This article will summarize the recent progress in engineering bacteria for the treatment of tumors.
2021, 10(4):102-114. DOI: 10.12146/j.issn.2095-3135.20210427008
Abstract:In recent years, research on the intestinal microbial communities and human health has developed rapidly. However, the regulation and application of the intestinal microbial community are still in their infancy. The reason for this is that our understanding of the structure and function of the human gut microbiome is inadequate. Synthetic microbiota is a new microbial community established by artificial synthesis of multiple species, which is simulated, tested, and optimized by various experimental models and mathematical modeling methods in vitro and in vivo. It is helpful to deepen the understanding of the structure, stability, and functional activity of the complex microbiota in the human gut. We summarized the research methods of the intestinal microbiome, the factors affecting the stability of the intestinal microbiome, and the challenges facing the synthesis of the intestinal microbiome, in order to provide a reference for the bidirectional transformation of the theoretical research and clinical application of intestinal microbial community.
2021, 10(4):115-125. DOI: 10.12146/j.issn.2095-3135.20210427001
Abstract:There are two trends in current microbiological research. First, researchers have increasingly realized that intestinal microbes, especially a large number of anaerobic bacteria, are closely related to human health with the development of intestinal microbe-related research. Because the intestine itself belongs to an anaerobic environment to a certain extent, the cell physiology research of intestinal bacteria needs to be based on the anaerobic culture environment. Second, it is difficult to meet the requirements of cell heterogeneity only by relying on classical microbial population culture methods. Research on heterogeneity requires the development of methods to study bacterial physiology at the single-cell level for in-depth study of the physiological laws that are hidden by cell populations and ignored by researchers. Here, a method is developed for culturing bacteria under anaerobic conditions, including the design of related culturing equipment and corresponding experimental procedures. Based on stably maintaining the strict anaerobic condition of the culture environment, the microfluidic chip is used to long-term singlecell culture. Combined with high-resolution microscope time-lapse imaging technology, the real-time observation and data collection of growth dynamics of single bacterial cell can be realized. This method provides powerful technical support for single-cell analysis of bacterial cells under anaerobic conditions.
2021, 10(4):126-136. DOI: 10.12146/j.issn.2095-3135.20210427007
Abstract:The lung is an important part of the human respiratory system, and the airway epithelium is the first barrier between the lung and the external. It is involved in defending against foreign particles, pathogens, etc, expelling foreign bodies as sputum and plays a vital role in maintaining the normal function of the respiratory tract. Commonly used in vitro cell culture models and mammalian models cannot fully simulate the human lung-airway microenvironment yet, and have limitations in the study of human cellpathogen interactions and drug development. In this research, we designed a microfluidic chip by improving the preparation process to meet the requirements of very short working distance of high magnification microscope for high-resolution imaging. The lung-on-a-chip reproduced the air-liquid interface airway epithelial culture, simulated human lung-airway microenvironment and obtained real-time observation of the co-culture process of cells and bacteria. It provides a powerful research platform for studying the interaction between airway epithelium and pathogenic microorganisms in vitro.