Synthetic Biology: What Does it Mean for the Pharma Industry?

An emerging branch of biology is opening the door to new possibilities in understanding diseases, with promising applications in drug development. The synthetic biology industry is expected to triple in size from $9.5 billion to $30.7 billion this year. Synthetic biology represents an innovative approach to redesigning organic biological systems for useful purposes, with an increasing number of applications across the pharmaceutical industry.

Synthetic biology has a number of definitions, but can be characterised as the redesigning and engineering of organic biological systems for useful purposes. This area of biology is built on a multidisciplinary approach, combining the expertise of biotechnology, engineering and science to develop “novel artificial biological pathways or synthetic biomolecules”. 

It is important to distinguish the difference between synthetic biology and genome editing. In synthetic biology, genetic engineering is constructed on a larger scale, in which scientists synthesise long sequences of DNA to form genes either found in other organisms or which are entirely novel. Genome editing, on the other hand, involves smaller changes within an organism’s own DNA – these changes can be deletions or inserting small DNA sequences into the genome. 

Synthetic biology offers a number of opportunities that could benefit the pharmaceutical industry in discovering new ways of treating diseases and accelerating drug development. 

Below are two of the main ways in which synthetic biology strategies are being implemented:

• Engineering biosynthetic pathways, gene networks, proteins, and molecular switches for optimising or enhancing natural cellular functions for in vitro or in vivo 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.

Both of these offer huge potential for drug development, especially so for precision medicine, which appears to be leading the way for drug discovery across the industry. In oncology the potential application for bespoke molecular switches could be huge for cell and gene therapy. In some cancer patients, alterations in the hosts’ genome predispose treatment resistance to conventional therapies. Hence, preclinical research investigating the efficacy of specific molecular switches could eventually lead to more effective, personalised cancer treatment.

In addition to more precise, personalised therapies, synthetic biology tools offer a number of other advantages. The production of novel bio-based drugs and treatment modalities could offer opportunities to treat a number of rare diseases and/or aim for previously undruggable targets. 

The design and synthesis of specific molecules, proteins for example, can also save pharma companies time and money by reducing the cost of drug discovery and development. The impact of this down the line is increased access to more effective, affordable therapies.  

Despite remaining a relatively novel approach to drug design, synthetic biology is becoming a growing presence in the pharma industry. Oncology CAR-T therapy is an example of treatment which utilises synthetic biology, engineering the immune cells (T cells) of patients to recognise and attack cancerous cells in the system. 

According to a 2019 study, one of the exciting opportunities synthetic biology could offer in the next few years is the production of theranostic cell lines that can sense a disease state and produce an appropriate therapeutic response. Theranostics is a “wide field in biomedical engineering involving in vitro diagnostics and prognosis”.

The growing of theranostic cell lines is one of the key trends in the growing potential of synthetic biology, according to a 2020 report. 

Synthetic biology in practice

AI drug design

In April this year, Exscientia announced the first AI-designed immuno-oncology drug to enter clinical trials. Drug design by AI has been a key area of focus for a number of pharma companies over the past few years, yet no one has reached the clinical stage until now.  

AI drug design is one of the many areas in which synthetic biology supports drug development. This approach utilises AI to address some of the challenges with current technologies which limit the drug development process, making it a time-consuming and expensive task. 

AI can recognise hit and lead compounds, and provide a quicker validation of the drug target and optimisation of the structure design. The systematic approach of AI towards target identification and validation results in this optimised drug design. One of the main advantages of this results in a drug which typically demonstrates higher selectivity for the target and fewer side effects and potential toxicity. 

These benefits are echoed in Exscientia’s press release, whose drug candidate for adult patients with advanced solid tumours “has potential for best-in-class characteristics, with high selectivity for the target receptor, bringing together potential benefits of reduced systemic sides effects as well as minimal brain exposure to avoid undesired psychological side effects.”

Of course there remains a number of potential challenges with this approach. Reproducibility for example, remains a major defect in AI technologies so far. In comparison with in vitro/in vivo designs, it is not possible to reproduce outcomes predicted by AI.This raises a number of red flags with regards to supporting the validity of the data and whether the output matches in the input. 

Another challenge is that it is not possible to account for hidden variables – a drug designed by AI may be unlikely to predict untargeted properties for confounders in the biological system. A potential solution to this is randomisation of the data.

Ethical implications

The ethical questions relevant to synthetic biology are similar to ethical discussions related to genome editing:

• Are humans crossing moral boundaries by redesigning organisms with synthetic biology techniques? 

• If synthetic biology yields new treatments and cures for diseases, who in our society will have access to them? 

• What are the environmental impacts of introducing modified organisms into the ecosystem? 

While the value of its applications and potential benefits so far are promising, the implementation of synthetic biology continues to raise concerns. Some question the potential ways of exploiting the field for dangerous use, like chemical warfare. Other concerns come from the ethical standpoint of ‘where do we stop’ – this has no doubt led to a number of discussions weighing up the ethical implications versus the potential benefit for patient populations.

As the field of synthetic biology grows, it will be exciting to see the future application of these technologies in research and drug development. The current regulatory process for areas like genome editing may be adapted to the application of synthetic biology – a method of justifying its use in terms of therapeutic benefits for patients, while monitoring its implementation from a safety standpoint and taking into account ethical considerations. 

Charlotte Di Salvo, Former Editor & Chief Medical Writer
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