Synthetic Biology Approaches in The Development of Engineered Therapeutic Microbes

Int J Mol Sci. 2020 Nov 19;21(22):8744. doi: 10.3390/ijms21228744.

Abstract

Since the intimate relationship between microbes and human health has been uncovered, microbes have been in the spotlight as therapeutic targets for several diseases. Microbes contribute to a wide range of diseases, such as gastrointestinal disorders, diabetes and cancer. However, as host-microbiome interactions have not been fully elucidated, treatments such as probiotic administration and fecal transplantations that are used to modulate the microbial community often cause nonspecific results with serious safety concerns. As an alternative, synthetic biology can be used to rewire microbial networks such that the microbes can function as therapeutic agents. Genetic sensors can be transformed to detect biomarkers associated with disease occurrence and progression. Moreover, microbes can be reprogrammed to produce various therapeutic molecules from the host and bacterial proteins, such as cytokines, enzymes and signaling molecules, in response to a disturbed physiological state of the host. These therapeutic treatment systems are composed of several genetic parts, either identified in bacterial endogenous regulation systems or developed through synthetic design. Such genetic components are connected to form complex genetic logic circuits for sophisticated therapy. In this review, we discussed the synthetic biology strategies that can be used to construct engineered therapeutic microbes for improved microbiome-based treatment.

Keywords: genetic engineering; synthetic biology; therapeutic molecules.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus / microbiology
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / therapy*
  • Disease Models, Animal
  • Dysbiosis / microbiology
  • Dysbiosis / pathology
  • Dysbiosis / therapy*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Fecal Microbiota Transplantation / methods
  • Gastrointestinal Diseases / microbiology
  • Gastrointestinal Diseases / pathology
  • Gastrointestinal Diseases / therapy*
  • Gastrointestinal Microbiome / genetics
  • Gene Regulatory Networks
  • Genetic Engineering / methods*
  • Humans
  • Lactococcus lactis / genetics
  • Lactococcus lactis / metabolism
  • Mice
  • Neoplasms / microbiology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Probiotics / therapeutic use
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Synthetic Biology / methods*

Substances

  • Recombinant Proteins