First, we need to unpack the words ‘synthetic biology.’ A good, concise definition is ‘the design and engineering of biologically based parts, novel devices and systems, as well as the redesign of existing, natural biological systems.’1 Note the key words design and engineering. The power of synthetic biology arises by bringing together biological research with the process of engineering.
The original ideas for modifying biological systems were developed more than 40 years ago, following the discovery of the structure and function of DNA. By using techniques such as restriction enzyme-based cloning, molecular biologists were able to ‘cut and paste’ DNA and thus modify the function of organisms.
From these first steps, the introduction of powerful engineering concepts to biology — such as abstraction, modularisation, characterisation, specification and validation — is of particular importance.2,3 This starts to allow biological systems to be deliberately designed and built to achieve certain desired characteristics in the same way we might design and build a computer from components — a very different approach from traditional biological research.
By taking this approach, we have the potential to address some of the most fundamental problems in the world today. As biological systems are globally ubiquitous, the ability to create desired characteristics can have a huge impact and outlines some of the application areas for synthetic biology across various industries and sectors.
The work in food, environment and fuels is attempting to find sustainable ways to feed and water the growing global population and provide for its energy needs — with a strong emphasis on sustainability. Nature is outstandingly good at building systems that recycle materials and minimise energy consumption from renewable sources (such as the sun). We can learn from these principles as we understand and engineer biologically based processes.
In particular, synthetic biology is starting to impact healthcare in many ways. Work is focused on a number of different areas, looking at both mammalian systems and at micro-organisms. Starting with mammalian systems, the main areas of application are gene-based therapies, in vivo diagnostics and disease models. The ability to reliably and rapidly make precise edits to a patient’s DNA supports techniques such as CAR-T therapies to fight cancer, in which the patient’s own T-cells are engineered to recognise and attack the cancerous cells.
Similarly, such precise modifications open up the possibility of turning cells into sensors that continually monitor and report on your health, particularly for chronic conditions such as diabetes and cancer. Drug development research is made easier by using synthetic biology to create modified cells that act as models for drug target testing; instead of waiting for a biopsy sample with unknown characteristics, you can create the test conditions you need.
Work in micro-organisms is looking at related areas. The microbiome — the organisms that inhabit the human gut and skin — is a hot topic presently as the intimate functional interaction between the micro-organisms and the human host to maintain health becomes clear. By engineering the microbiome, you can monitor and manage the health of the host.
Another use of micro-organisms is in vaccine and therapeutic delivery, developing methods to introduce such molecules effectively to the body in oral formats. Finally, micro-organisms are also being investigated to manufacture drugs and precursor molecules. By engineering optimised metabolic pathways in yeasts or bacteria, you can create high efficiency, high quality methods to manufacture complex molecules — the so-called ‘bugs as factories’ approach.
The vision of rationally engineering biological systems is becoming ever more real today. This is because of the increase in tools available to support the approach. These tools cover a wide range:
- Low-cost, easy-to-use biological tools such as CRISPR/Cas9 gene editing reagents allowing rapid and precise reprogramming of sequences. Tools such as this have turned post-doc-level protocols into methods a high-school student can execute.
- Low-cost, high-fidelity de novo DNA synthesis, allowing any desired DNA sequence to be created. This brings a new freedom — particularly for variant libraries — as you are no longer constrained to create your desired sequence by laboriously editing and assembling existing sequences.
- Very low-cost rapid DNA sequencing with the computing and analytical capacity to make sense of the data produced. Sequencing DNA is now easy and routinely done, which supports numerous methods to measure the functions of biological systems.
- Sophisticated software tools to design DNA sequences, predict their performance in the biological system and define how to assemble them. These are exciting as they are driving the core concept of moving towards the rational, predictive design of biological systems instead of trial and error.
- Next-generation lab automation tools in both hardware and software, allowing easy design, execution and analysis of large, complicated experiments. This includes ‘cloud labs’ where scientists can submit their experiments to centralised automated equipment using a web-based interface and a standardised language to describe the experimental process.
The financial investment in synthetic biology tools and products is also increasing rapidly; 2015 was a record year for investment, with $803 million invested into synthetic biology start-up companies globally. However, more than $828 million was invested in the first half of 2016 alone, with healthcare companies taking a large share of this investment.4 Established companies are also taking a strong interest and starting to bring synthetic biology approaches and ideas into their organisations.
Conclusion
Synthetic biology provides a new approach to drug development and delivery. It is, at heart, an engineering discipline focused on specifications, design, characterisation and quality … but underpinned by elegant, subtle and powerful biological functions. It has huge potential and is rapidly becoming a real, commercially relevant technology. Such a powerful technology with great potential will inevitably become a mainstream discipline for the coming century.
References
1. A Synthetic Biology Roadmap for the UK: www.rcuk.ac.uk/documents/publications/syntheticbiologyroadmap-pdf (2012).
2. www.nature.com/nbt/journal/v26/n7/abs/nbt1413.html.
3. http://shop.bsigroup.com/ ProductDetail/?pid=000000000030303883.
4. synbiobeta.com/news/reviewing-synbio-startup-scene-2016.
