Applications of Synthetic Biology in Pharmaceuticals and Therapeutics

Among the vast number of areas benefiting from synthetic biology, medicine is rapidly taking the lead in adopting the novel tools and strategies developed by this discipline. Engineered cells capable of integrating multiple inputs and discriminating between cell states or types, or producing desired proteins for targeting diseased or foreign cells are revolutionizing the way known or emerging diseases are treated. Biological systems engineered by synthetic biologists are employed in different aspects of medicine, from drug discovery to developing cell-based therapies for personalized medicine and biologics replacing chemically-synthesized drugs. With several successful applications coming to market, more synthetic biology-based solutions are expected to move from concepts or laboratory testing to clinical trials and FDA approval.

• How is synthetic biology advancing medicine?

  Synthetic biology strategies are fast advancing the frontiers of medicine through:

  • Engineering biosynthetic pathways, gene networks, proteins, and molecular switches for optimizing or enhancing natural cellular functions for in vitro or in vivo medical applications;
  • Engineering naturally-existing bacterial, viral, plant and mammalian cells or constructing new cellular entities (i.e. cells or organisms) de novo for obtaining novel functional outputs with therapeutic applications.
• What is the advantage of applying synthetic biology strategies for developing pharmaceuticals and therapeutics?

  By adopting synthetic biology tools and strategies, we can:

  • Improve the efficiency of the traditional drug discovery process;
  • Enable the production of novel bio-based drugs and treatment modalities for common, rare or emerging forms of disease;
  • Save time and money through reducing the cost of drug discovery and development;
  • Increase access to effective and affordable treatments;
  • Offer precise and personalized therapies to each patients;
• What are some of the examples of drugs and therapies developed by synthetic biology strategies?

  Armed with the massive data generated by basic life sciences research on the biology and pathology of cells at the cellular and molecular level, synthetic biologists have so far helped to revolutionize medicine in the following categories:

  • Drug Discovery: Synthetic biology is reorienting all steps of the drug discovery process from hit finding and lead generation to ADME (absorption, distribution, metabolism and elimination or excretion). This is achieved through designing engineered genetic circuits in host organisms to increase the influx of secondary metabolite pathways, protein engineering to explore the chemical diversity of secondary metabolites, development of optogenetic biosensing for target validation and understanding drug’s mechanism of action and delivery, and utilizing cell-cell communication and quorum sensing to overcome drug resistance, optimize secondary metabolism and fight toxic effects.
  • Delivery & Monitoring of Therapeutics: Typical routes of administrating drugs are often associated with deleterious side effects to healthy tissues. Novel synthetic biology approaches are leading to the development of programmed forms of drug delivery that release the right dose of the drug upon sensing a pathological state. Similarly, with the help of synthetic biology strategies, monitoring the pharmacodynamics and pharmacokinetics of therapeutics are reaching to new standards of sensitivity and efficiency. Examples include an orally-administered, engineered bacteria that excretes disease-specific drugs in the GI tract, and prosthetic devices consisting of transplantable, microencapsulated mammalian cells equipped with synthetic gene circuits or assembled signaling pathways for restoring chemical homeostasis in metabolic diseases. Engineered DNA nanostructures are also used for monitoring drug metabolism in vivo.
  • Biosynthesis of Pharmaceutically Active Compounds: Synthetic biologists are using two approaches for making drugs that have traditionally been made through chemical processes or extracted from plants. The first approach involves the assembly of complex metabolic pathways in microorganism. Production of the anti-malaria drug artemisinin from engineered yeasts and the anti-cancer drug Taxol are prime examples of this approach. The second approach involves the use of non-natural amino acids and expanded genetic code for the biosynthesis of peptide-based compound libraries for functional screening of drugs.
  • Vaccine Development: With the growing worldwide demand for vaccines to prevent infectious diseases and emergence of new strains of infectious agents, synthetic biology is offering solutions for developing cost‐effective and efficient strategies for vaccine development. Examples include engineered peptide, DNA and RNA vaccines produced in natural or engineered host organisms, animals and plants.
  • Developing Alternative Therapies: Synthetic biology is enabling the development of numerous forms of alternative therapies which could only be conceptualized a decade ago. The following lists the major categories of such therapies:
  • Gene Therapy: Engineered bacteria and viruses, containing a rationally-designed network of natural and synthetic genes, are constructed such that they can only replicate in cancer cells and lead to their destruction upon lysis. In another example, based on synthetic genetic elements or chimeric regulatory proteins, simple genetic circuits are devised in insects such that the propagation of engineered insects can lead to the eradication of parasite-carrying insect populations. Gene therapy can also be combined with autologous cell transplantation where engineered stem cells are used to treat inherited diseases.
  • CAR-T Cell Therapy: As a revolutionary form of therapy, the ex vivo engineering of T-cells from a patient followed by its transfer to patient’s body allows for targeted therapy of cancer cells with no other available form of effective therapy. A more recent advancement in this area is the combination of this therapy with AND logic systems that allows dual recognition of cancer markers to confer is further specificity to this novel mode of therapy.
  • Protein-Based Therapies: Naturally occurring proteins like growth factors and synthetic antibodies belong to this category of therapeutics. These therapies work through cell surface receptors to modulate the activity of signaling pathways. By testing combinations and variants of engineered therapeutic proteins, synthetic biology improves the efficiency and specificity of protein-based therapeutics. Compared to nucleic acid- or cell-based therapies, this form of therapy has the advantage of local and transient administration as well as skipping the safety concerns associated with genomic manipulation strategies.
  • Biomaterials: The convergence of synthetic biology and material science had led to the development of novel biomaterials with important applications in health care and medicine. Such biomaterials can serve as implants for supporting cellular transportation of therapeutics and enhancing tissue regeneration. Biomaterials can also be used to encapsulate genetically-modified cells as an alternative form of therapeutic gene circuit delivery to provide safety from potential immunogenic side effects.