Applications of Synthetic Biology in Developing Diagnostics

Addressing modern medical needs, including precision medicine, requires innovative solutions to robustly detect, monitor and even interface patients’ pathophysiology. Unfortunately, conventional diagnostics, which are based on pre-genomic era technologies, often fail to provide clinically informative results to meet such needs. With the increasing application of rational and systemic biological design in development of diagnostics, however, we are seeing breakthrough solutions for overcoming existing challenges and enabling precision medicine.

Synthetic biology-based diagnostics provide real-time, dynamic, sensitive, highly-specific, and non-invasive methods for detecting and monitoring cancer cells, metabolic parameters, infectious agents, therapeutics, and exposure to toxins. Development of dual-functioning diagnostic-therapeutic platforms are also changing the definition and application of diagnostics in medicine towards a more comprehensive and integrated approach in patient care.

• How does synthetic biology help with the development of diagnostics?

  Synthetic biologists are using rational engineering strategies to make novel biosensing systems that are modular and comprised of a:

  • sensor: detects desired signal(s) from in vitro or in vivo environments;
  • processor: a simple or multiplex synthetic circuit capable of processing received signals, integrating them with medical knowledge, and classifying patient conditions into clinical categories;
  • reporter: displays assay results as chemical, biological, electronic or combination outputs.

  These synthetic systems can be built in different formats as individual diagnostic or diagnostic-therapeutic assays/devices, or integrated into conventional assays/devices:

  • In vitro assays: comprised of synthetic genes and oligonucleotides, synthetic multifunctional antibodies, or multi‐epitope and chimeric antigens printed on paper or integrated into conventional testing platforms for probing or detection purposes;
  • In situ biosensors: developed as DNA nanostructures or cell-based biosensors of bacterial, yeast, or mammalian origins carrying prosthetic networks that can be used individually or integrated into portable or implanted devices for collecting functional and physiological information.
• What is the advantage of applying synthetic biology strategies in diagnostics?

  Application of synthetic biology strategies in diagnostics industry offers the following benefits:

  • Enables development of portable, implantable, low-cost, versatile, accessible, highly scalable and versatile assays;
  • Allows for precise processing of localized cellular and molecular information in clinical settings where such data is critical to patient’s survival;
  • Allows for high-throughput detection of different strains of infectious agents from a single drop of raw body fluids;
  • Helps avoid issues with reproducibility, bulky experimentation, patient discomfort, centralized (i.e. laboratory setting) sample and data collection, long and tedious cultivation and analysis processes, as well as poor correlation with clinical symptoms;
  • Provides timely detection and response to emerging infectious diseases and global epidemics;
  • Allows for complex measurements while significantly improving and speeding up diagnostic to treatment efficiency;
  • Enables continuous monitoring of patient’s pathophysiology and/or response to therapeutics in vivo.
• What are prime examples of synthetic biology-based diagnostic?
  • Encapsulated pancreatic islet cells for sensing blood glucose levels and secreting insulin in a rat model of diabetes
  • Engineered E. coli capable of assessing tumor microenvironment to detect liver cancer in urine
  • Personalized and precise profiling of allergies in human whole‐blood samples through embedding a synthetic G‐protein signal processing module in engineered mammalian cells
  • DNA origami nanostructures used as malaria or heart failure diagnostic tools
  • Generation of chimeric antigens that are specific to a disease status or pathogens in serum-based diagnostic assays