Traditional small molecule drug discovery has dominated pharmaceutical R&D for more than a century, but the field has become increasingly more challenging as novel, efficacious applications for universally effective therapeutics have been nearly exhausted.1 As the world’s population continues to increase, along with the number of patients with documented diseases, the drive for precision medicine is even more urgent.
The future growth of the small molecule sector has likely been reduced to the discovery of new drug targets that result from a deeper understanding of various diseases and new ways of targeting specific subpopulations of patients.1 Biotherapeutics is bridging the gap in traditional discovery pipelines because of its ability to provide greater specificity and the promise of combatting previously untreatable diseases. However, commercialization of biotherapeutics presents ongoing challenges, in part, because the requisite biological molecules cannot be produced with the purity or quantity required for large-scale production.1 Biotherapeutics generally rely on inserting genetic elements encoding a peptide, protein, or antibody of interest into a host organism capable of producing it in large quantities, and the resources required to scale production can make scalability economically unviable.1
Enter Synthetic Biology
Synthetic biology offers novel approaches for engineering new biological systems or re-designing existing ones for useful purposes.2 It has been described as a disruptive technology capable of delivering new solutions across a variety of industries. The field of synthetic biology has united a diverse community of interdisciplinary researchers and societal stakeholders over the last 20 years, and its potential use cases go well beyond medicine. Experts across molecular biology, biochemistry, biophysics, and social sciences are working to integrate their findings into an engineering-design framework, with the goal of safe and ethical development of cutting-edge biotechnologies that can help address a variety of societal challenges. By rationally engineering or repurposing biological parts, devices, and systems, scientists anticipate a positive impact across a broad range of industries, spanning medicine, food, sustainable energy, bioremediation, education, and biomanufacturing. Despite its potential to treat diseases and solve resource scarcity, there are concerns that synthetic biology can be used for nefarious purposes, such as chemical and biological threats,and governments and regulatory bodies are working with the scientific community to ensure that infrastructure is in place to safeguard against misuse of this dynamic technology.
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Cell-Free Synthetic Biology and Genetic Engineering
Synthetic biology and traditional genetic engineering operate along the same continuum. Where genetic engineering may manipulate the expression of a single gene, synthetic biology aims to go much further; it incorporates systems data (such as transcriptomics, proteomics, and metabolomics) and mathematical modeling into experiments with the eventual goal of possessing biological blueprints that allow scientists to understand and modify an organism.4 In other words, synthetic biology is the deliberate, rational engineering of living systems that produce specific, human-designed outputs with predictable properties and functions.3Cell-free synthetic biology is a broad term that spans a variety of in vitro biotechnologies.3 On a high-level, the term refers to different methods and technologies for engineering or using biological processes outside of a cell.3 For example, cell-free protein synthesis reactions enable protein production within biochemical reactions, allowing for isolated cellular components (e.g., recombinant proteins) and/or cell extracts, rather than live whole cells.3 While the design, synthesis, and expression of DNA are important, the process of standard genetic engineering is not typically under the same level of scrutiny and regulatory control, because endeavors in synthetic biology have more far-reaching implications for society at large.4
Applications in Medicine
Recent developments in synthetic biology have the potential to transform healthcare. Patients are already benefitting from CAR (chimeric antigen receptor) technology, which engineers the immune cells (T cells) of the patient to recognize and attack cancer cells.3Additionally, researchers are using genetically engineered viruses to correct deficient genes in patients with inherited diseases, like severe combined immune deficiency (SCID) and epidermolysis bullosa.3
Synthetic biologists can also reprogram and transform patients’ cells into stem cells, which not only furthers understanding about certain diseases, but also reduces the use of animals in medical research.3 These advancements pave the way for the development of personalized medicines and cell therapies. In theory, scientists could engineer a patient’s own cells to multiply, differentiate into specific cell types, and group together into new tissues (or even organs) to repair those damaged by sickness or injury.3
Furthermore, work in synthetic biology is helping to produce more streamlined therapeutics and vaccines with fewer side effects and a reduced risk of resistance.3 As an example, new vectors are able to deliver large genetic loads to target specific tissues.3 Scientists are also finding ways to optimize vaccine or antibody production by developing treatments that are edible (plant-based) — utilization of such technology could theoretically be leveraged for vaccines in future pandemics, greatly reducing costs, increasing manufacturing volume and efficiency, and facilitating seamless administration.3
Risks and Government Regulation
As synthetic biology is a relatively new, emerging field, much remains unknown about the processes and products that it can produce. Given the uncertain nature of the technology, governments in the United States, the European Union, and Singapore have called for a collaborative and multi-institutional approach to govern these emerging technologies.6 Policies must focus on mitigating public health concerns, with special attention paid to the potential for accidental events during the development process as well as an emphasis on biosecurity — embedding protective measures into R&D and immediately flagging the deliberate misuse of technologies for sinister purposes.6
It is possible that the release of genetically modified organisms can cause significant and irreversible harm to humans, animals, and the environment — examples include threats to biodiversity, where modified organisms unintentionally outcompete their native counterparts — or horizontal gene transfer, where artificial genetic information is transferred from an engineered organism into an unintended native host.6 To prevent such instances, current regulations around synthetic biology includes safe containment and control procedures for genetically modified material, including safe laboratory and manufacturing processes, controls on imports and exports, and proper containment for shipment and field release, commercial consumption, and end-of-life disposal.6
Beyond Pharma
Developments in synthetic biology also have the potential to revolutionize the future of other industries, from food to fuel. The effective merging of food science and synthetic biology is not only important for solving the existing problems of food safety and nutrition; it may be needed to overcome the sustainability issues associated with traditional food technology.7 By constructing enhanced cell factories using synthetic biology, food producers can create products such as artificial meats, animal-free bioengineered milk, and sugar substitutes using only renewable resources.7 Overall, applying synthetic biology to food science can remove many of the drawbacks associated with traditional agriculture, preserving an abundance of resources.
With population growth, climate change, and decreasing finite resources, demand for food, water, and energy will soon exceed supply.7The human population is predicted to exceed 11 billion by the year 2100, and, with fossil fuel reserves depleted, the importance of agriculture to produce non-food items (like fuels, fibers, and platform chemicals) will only increase.4 However, recent breakthroughs in plant synthetic biology may offer solutions, primarily through increasing crop yields to meet these demands. An example of this is a complex polyphenolic network found in some secondary plant cell walls called lignin — it is typically difficult to break down and process as part of biofuel production. However, developments in synthetic biology allow the production of “designer lignin,” which makes the lignin more usable in biotechnical applications without affecting crop yields.4
Synthetic biology can also contribute to creating platform chemicals: the building block molecules from which most plastics are produced.4 Scientists and business leaders alike are looking to create alternatives from renewable resources like plants to make sure material production across industries is sustainable. Using synthetic biology, scientists have already produced muconic acid — a precursor for bulk chemicals in nylon, polyethylene terephthalate (PET), and polyesters — in a range of microbial systems, including Escherichia coli.3
Economic Landscape
Synthetic biology startups and small-to-medium enterprises have already begun to commercialize products and services. To date, the bulk of funding has been in healthcare applications, but the stage is set for many more developments to come to market.5 Government policies and increasing consumer awareness surrounding sustainability problems will only continue to drive the development of synthetic biological applications for commercial use. The rate of commercial translation of synthetic biological developments is influenced by several national, cultural, and operational differences. As of 2019, 80% of the academic research publications in synthetic biology by the Web of Science were generated by authors from just four countries: the United States, China, Germany, and the United Kingdom.4Overall, the synthetic biology industry has attracted more than $12 billion in investments over the past decade, predominantly within the U.S. and the UK.5 Of the 176 U.S. or U.K. startup companies, almost half (48%) of the investments are in health, followed by tools and services (24%), industrial (11%), food (10%), and agritech (7%).5
Final Thoughts
Advancements in synthetic biology are transforming the capability to design and engineer biological systems for healthcare, industrial, and commercial purposes. As sustainability challenges escalate, the field will play a vital role in making sure that medicines, fuels, and food can be produced in an efficient and sustainable manner. Synthetic biology has the potential to disrupt several industries; however, to ensure safe development and application, world governments and private organizations must be diligent in creating effective safety measures.
Researchers and government officials from around the world met at the University of Edinburgh in 2018 to discuss synthetic biology, and key takeaways included the need for larger investment in better big data management and processing; standardization initiatives; the creation of a universally targeted overarching goal; improvement of assessment, communication, and management of risk and harm; ensuring that early career researchers are trained in responsible research conduct and ethics as well as being cognizant of existing rules and regulations; and the need for alignment across academia, government, and industry through focused meetings that foster interdisciplinary collaborations around shared objectives.2
There is much work to do to make synthetic biology a truly disruptive force in the future, but with proper infrastructure, it can potentially solve many current and future problems as the world population continues to grow.
References
McElroy, David. “Biopharmaceutical Manufacturing and the Power of Synthetic Biology.” Biopharm International. 30 Apr. 2020. Web.
El Karoui, Meriem; Hoyos-Flight, Monica; Fletcher, Liz. “Future Trends in Synthetic Biology—A Report.” Frontiers in Bioengineering and Biotechnology. 7 Aug. 2019. Web.
Kelwick, Richard J. R.; Webb, Alexander J.; Freemont, Paul S. “Biological Materials: The Next Frontier for Cell-Free Synthetic Biology.” Frontiers in Bioengineering and Biotechnology. 12 May. 2020. Web.
Mortimer, Jenny C. “Plant Synthetic Biology Could Drive a Revolution in Biofuels and Medicine.” Sage Journals. 24 Sep. 2018. Web.
Clarke, Lionel; Kitney, Richard. “Developing Synthetic Biology for Industrial Biotechnology Applications.” National Institutes of Health. 20 Feb. 2020. Web.
Trump, Benjamin D. “Synthetic Biology Regulation and Governance: Lessons from TAPIC for the United States, European Union, and Singapore.” Science Direct. Nov. 2017. Web.
Lv, Xueqin; Wu, Yaokang; et al. “Synthetic Biology for Future Food: Research Progress and Future Directions.” Science Direct. Jun. 2021. Web.
