Using Synthetic biology to Combat Pandemics: What? Why? How?

The smallpox vaccine was the first vaccine developed by Edward Jenner in 1796. Vaccine science since then has developed tremendously. Vaccine development is a multistep, multi-month process. However, the unmitigated threat of COVID-19 has demanded novel synthetic biology solutions to develop vaccines, diagnostics, and treatments. Harnessing synthetic biology for combating the current outbreak of SARS-CoV-2 has not only lead to the rapid advancement of vaccine technology and diagnostics tests but has also opened new horizons for combating future pandemics. 

Synthetic Biology Basics

The genome is the complete set of DNA in an organism. In the last few decades, scientists have mastered the techniques for reading DNA, putting the readout in a specific order of As, Cs, Ts, and Gs for an organism. Scientists now have been able to print the DNA molecules as well as edit and program the DNA. These breakthroughs have pioneered the way for the development of synthetic biology. In simple terms, synthetic biology could be defined as, “ systematic edifice of new or existing biological systems for a valuable function”. It is a nature-based design and has applications in multiple fields ranging from food technology, diagnostics tests to vaccine development. Rather than being a branch of a specific field, synthetic biology is a multi-disciplinary field comprising of biology, engineering, genetics, chemistry, molecular biology, cell biology, biophysics, evolutionary biology, and computer science. 

The global synthetic biology market is divided into product type, technology, application, and region. Further, based on the type of products it gets segmented into oligonucleotides, synthetic genes, synthetic DNA, genetic modified organisms, synthetic cells, and software tools.

While synthetic biology has wide-spread applications and uses, this article will focus on applications in diagnostics, vaccine development, and therapeutic advancement.

Synthetic Biology in Diagnostics

The current coronavirus outbreak demands enhanced application of synthetic biology for the rapid development of diagnostics tests. The 2019-nCoV is difficult during the first two weeks of infection. Conventional diagnostic tests rely on antibody-based detection approaches, while these are sensitive, they are slow and expensive to produce. The COVID-19 pandemic has proved the need for rapid and cost-effective detection tests. Synthetic biology approaches offer to overcome these limitations with their rational and short design-to-production cycles.  

Diagnostic tests including the Toehold circuits, in vitro CRISPR-based detection kits, qRT-PCR detection assays. The World Health Organization (WHO) has recognized the RT-qPCR test with standard and confirmed primers and probes for sensitive and rapid detection of 2019-nCoV. GenScript freely offers researchers all over the world a high-tech test for coronavirus detection based on qRT-PCR detection assay. For example, this test uses RNA from the virus for accurate detection and quantification of the viral load in the bloodstream. 

Synthetic biology offers avenues to combat current as well as future pandemics. The devices such as engineered genetic circuits expand our capabilities in the field of molecular diagnostics as well as the molecular detection capabilities by aiding in the design of dynamic sensors. In the future, synthetic biology possibly will offer tools for in vivo diagnostics providing real-time surveillance for multiple pathogenic conditions. 

Synthetic Biology in Vaccine and Therapeutic Development

Scientists have been using modified pathogens, such as the chickenpox virus to improve health in form of vaccines. Vaccines enable us to develop immunity and prevent illness upon infection by the real pathogen. During a virus outbreak, it takes months for scientists to access physical samples of the virus, causing researchers to lose critical response time. Synthetic biology offers a robust solution to this issue. The use of a synthetic clone of an infectious virus has helped researchers all over the world to start research without delays. Synthetic biology offers scientists a unique advantage, manipulation of the cloned DNA to understand the viral genes that influence virulence. Another advantage is that researchers can carry out in silico analysis to predict protein sequences for the development of effective epitopes or nanoparticles for mounting a robust immune response. Synthetic biology has also enabled scientists to build genome constructs using the genome assemblies of SARS-CoV-2 for ideal vaccine constructs. 

Multiple companies are in the race for the development of the SARS-CoV-2 vaccine. The mRNA-based vaccine is the front runner in this race and not far behind is a DNA vaccine. The speed at which companies have been able to come up with nucleic acid platforms for vaccine development highlights another benefit of synthetic biology- the ease with which DNA/RNA constructs based on the virus genetic sequence or more specific spike protein sequence can be designed and produced. The synthetic biology technologies have allowed researchers to safely conduct research avoiding the risk of working with live viruses. GenScript has synthesized genes of nCoV-2019 upon requests of labs all around the globe. The synthetic biology community has made biology easier to engineer.

Despite the benefits that synthetic biology has to offer in terms of effective and rapid vaccine development some concerns need to be addressed. It is important to consider the potential risks in terms of the absence of data during the clinical trial design of synthetic vaccines.

Future of Synthetic Biology

There is zero doubt that synthetic biology technologies will influence the next revolution in the pharma and biotech industries. Synthetic biology presents us with limitless possibilities in terms of engineered microbes for the management of environmental pollutants, production of biodegradable polymers, development of patient-specific therapies, medicine producing bacteria, in vivo diagnostics. Synthetic biology will potentially transform our response in combating future pandemics. Unleashing the full power of synthetic biology with appropriate regulations and checks will gear our society towards a healthier and safer future.

References:

• Synthetic biology devices for in vitro and in vivo diagnostics. Slomovic et al. PNAS. 112 (47) 14429-14435 (2015).
• Synthetic evolution. Simon et al. Nature Biotechnology. 37, 730–743(2019)
• Genome editing by natural and engineered CRISPR-associated nucleases. Wu et al. Nature Chemical Biology. 14, 642–651 (2018)
• Beyond editing to writing large genomes. Raj Chari & George M. Church. Nature Reviews Genetics. 18, 749–760 ( 2017).
• Synthetic biology to access and expand nature's chemical diversity. Smanski et al. Nature Reviews Microbiology 14, 135–149 (2016). 

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