You know the world is truly advanced when someone has invented a synthetic cell. And this happened five years ago. Enter the field of synthetic biology, defined as the use of molecular biology tools and techniques to construct genetic systems that produce a desired behavior.
With the decreasing price of DNA sequencing and synthesis, the ease of genetic engineering (CRISPR, molecular cloning), and the increase in computational capacity, we have reached a stage where creating an engineered cell, and making it do what you want is a possibility. Rooted from the discovery in 1961 by Jacob and Monad that bacteria have regulatory systems and circuits that control its interaction with its environment, the wide-spread use of ‘omics’ technology that followed allowed us to understand these circuits in detail. The subsequent rise in molecular engineering prowess – molecular cloning, recombinant technologies, gene editing, inducible promoters, light-sensitive promoters – has equipped man with the ability to engineer synthetic signalling pathways in the cell.
As understanding grew on how simple organisms such as bacteria, viruses and yeast sensed the environment and regulated their circuitry to respond to changes, scientists slowly found ways to produce sometimes entirely artificial circuits into these organisms, hijacking their systems to help man conquer even greater heights. Bacteria and viruses have been engineered to invade cancer cells, disperse biofilms, produce biofuel and synthesize drugs.
The main obstacles faced were designing parts of the circuit to talk to each other effectively, and making sure they work as designed in their specific context/environment. This was initially challenging but is getting easier with the ease of gene assembly, where whole genes can be synthesized by assembling short oligos together, allowing to build any circuit component independently. This is how Craig Venter created the first synthetic cell, assembling chemically-synthesized oligos into DNA chunks that were recombined in yeast to create an entire synthetic genome that was transplanted into a recipient bacterial cell that took on characteristics defined by the synthetic genome.
An up and coming biotech dealing in synthetic biology is Synlogic, founded by James Collins (Boston University) and his previous post-doc, Timothy Lu (MIT) in 2014. Their work focuses on developing therapeutic microbes which we ingest – that are engineered to interact with the gut microbiome to fight infection and chronic disease. The biotech has already accumulated $35 million in funding from investors which include the Bill and Melinda Gates Foundation, New Enterprise Associates and Atlas Venture. What’s more they recently snagged ex-Pfizer Senior VP and Head of Biotherapeutics R&D, JC Gutiérrez-Ramos as their CEO. Chief Scientific Officer Paul Miller is also a big pharma bigshot, serving as VP in Astrazeneca and before that in Pfizer. Alison Silva heads operations, previously also working for a biotech that dealt with engineered microbes. Though still in the early stages, the company has already presented in vivo efficacy data in its two lead programs targeting the orphan genetic metabolic conditions Urea Cycle Disorder (UCD) and Phenylketonuria (PKU). The details are not public but these synthetic microbes presumably detect changes in the gut microbiome and may even kill toxic cells.
Synthetic biology marries biology and engineering and scientist with mad skills in engineering genomes, building cellular circuits and understanding cellular systems would likely be in demand in years to come. So think big and stay friendly with bacteria.
D. Ewen Cameron, Caleb J. Bashor & James J. Collins “A brief history of Synthetic Biology” Nature Reviews Microbiology 12,381–390 (2014) doi:10.1038/nrmicro3239