Synthetic Biology is one of the most rapidly growing areas of science today, estimated to be worth US$13.4 Billion by 2019ƚ. So how do we define such a rapidly evolving field? To side-step any inference that our knowledge here supersedes that of the Industry itself, where numerous descriptions have already have been put forward* we have simplified the definition to that seeming most at its core in that it is applying fundamental engineering principles to biological processes; in turn creating efficiencies and novel applications or models.
DNA carries the genetic instructions for all known living organisms and many viruses. Our fascination to change this code began its journey in 1972 when Boyer and Cohen introduced recombinant DNA into a bacterial cell; two short years later the first transgenic mouse was created by Rudolf Jaenisch and genetic engineering was born. Over the last 50 years or so our ability to manipulate and, as equally important, to analyse the sequence of the genome has gathered speed and the emergence of new technologies, such as CRISPR, Sanger and Next Generation sequencing, means we have few limits. Where once the synthesis of DNA itself was a limiting factor, the advent of synthetic DNA and gene editing means that this is no longer the case. Unsurprisingly, Biotech companies have been quick to capitalise by commercialising molecular tools and research models giving the researcher unprecedented access to the genome.
Proteins are the work horse of the organism; they are required for the structure, function, and regulation of the body’s cells, tissues and organs. Designer proteins therefore come in several forms; natural proteins which have been genetically engineered to adapt or optimise function, and synthetic proteins that are able to recapitulate the structure and function of their ‘natural’ homologues. In 2011 Michael Hecht led his team from Princetown University to designed synthetic proteins which, for the first time, were able to sustain the growth and life of bacterial cells (Fisher et al.) and now we enter a truly exciting era for this field at a time which promises new solutions across Life Science in its entirety including renewable energies, vaccine development, therapeutics and targeted medicine.
Cells are the current building blocks of life from which we can build complex tissues and organs and from a design perspective two strategies can be employed; bottom-up or top-down. Top-down strategies take a parent cell and manipulate it through genetic or protein engineering, with the resultant synthetic cell being closely related to its ancestor biologically. The construction of a top-down synthetic cells focuses on building using a minimal genome approach, where the cell’s DNA is pared down to those essential for life. Conversely, the bottom-up approach starts with non-living material, and cell-like functionality is added by creating functional modules, designed from natural or artificial molecular building blocks. The components to a bottom-up artificial cell, are cell membranes, information carrying molecules and metabolic systems. During the design process genes are defined as biological units, units are combined such that functional modules are created. The DNA is then synthesised and encased in a vesicle. The metabolic systems require enzymes and energy, the energy is usually supplied from the environment thus the cell membranes must be permeable. Phospholipids are used to construct the artificial cell membranes. The aim of the bottom up strategy is to design a truly artificial cell, this is extremely challenging area of synthetic biology and, as yet, this has not been achieved so this remains an aspiration and future milestone within synthetic biology. However, it is the combination of these two strategies that will provide a more complete future toolbox within this field, thus, enabling the intricacy of the synthetic cell to be created in a step-wise manner. Also being developed of course, and something we’ll be keeping a close eye on at BioTechScope, is bioprinting where tissues and organs have the potential to be recreated through 3-d printing; an attractive point here being the structural sophistication of tissues and organs created this way. Although the first 3-d transplanted organ is probably still a way off, Organovo, a company based in San Diego printed the first human liver in 2013. Several other 3-d printed organs have followed and although not of transplantable quality, they are providing valuable insights into development and drug testing.
Synthetic biology offers potential for a cleaner, healthier future through improved clinical outcomes, biofuels, artificial food, genetically modified crops and consumer products manufactured from synthetic leather. So what can we expect from this field in the years to come?
In Healthcare, our wish list is likely to address synthetic stem cells, fully functioning synthetic replacement organs, disease and personalised treatment regimes. Whether it is nanoparticle chemical delivery systems which deliver a targeted approach to treatment, providing a more effective and less painful patient experience. Or the use of nano-factories; synthetic cells that produce anti-cancer proteins within the tumour tissue, designed to eradicate the cells. Immunotherapy, synthetic virology, designer drug delivery vehicles, along with gene therapy and personalised treatments are driving the translation of research and development into the clinic. The recent approvals by the FDA for several gene-editing trials to go-ahead, herald the way for this translation. However, the path to this may not be smooth and reports of the first HIV resistant genetically-modified babies from China in November 2018 may accelerate our thinking about how far we’re prepared to take some of these models from an ethical perspective.
With disease in mind, the introduction of organisms containing gene drives (genetic engineering technology that increases the probability of a gene being inherited) into the environment could provide a real answer to the spread of certain diseases. This technology is designed to rapidly spread through populations and has the potential to eradicate diseases such as malaria, control pests or even enhance the resistance of endangered species. However, as seen with other introduced species the consequences can be unpredictable and often disastrous. This is a contentious issue and the recent success of gene drives in mammals may give us food for thought, learning how to control and possibly reverse them may be crucial in their successful use in the wild. Indeed, the New Zealand government thinks this is the way forward. Predator Free 2050 is their proposal to eradicate introduced species from New Zealand by 2050 with gene drives forming an important part of the plan.
Environmental solutions will also be at the top of the list and the recent discovery and enhancement of plastic-digesting enzymes by a UK-USA enzyme engineering team provides a promising opportunity for addressing plastic load across the globe. Synthetic biology is also aiding bioremediation. A process whereby introduced engineered microorganisms breakdown environmental pollutants with enhanced oxidative enzymes. Biofuels are hoped to offer a tangible solution to ease the renewable energy and ecological pressure. Whether it is editing the genome of sugarcane to produce ethanol for biofuels (and bioplastics), the of use synthetic biology to create hydrocarbon farnesene from yeast, or engineering microalgae these examples are being optimised to produce a sustainable, high yield, ecologically superior fuel.
ƚ Transparency Market Research
* Nature journal reports it to be “the design and construction of new biological parts, devices, and systems, and the re-design of existing, natural biological systems for useful purposes”. The Royal Society similarly says “Synthetic biology is an emerging area of research that can broadly be described as the design and construction of novel artificial biological pathways, organisms or devices, or the redesign of existing natural biological systems.”