关键词: 微生物, 合成生物学, 活体生物药, 微生物细胞工厂, 疾病诊疗

Abstract:

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.

Key words: microorganism, synthetic biology, live biotherapeutic product, microbial cell factory, disease diagnosis and treatment