Introduction
Picture a time when we could programme living cells to effectively combat illness or produce necessary medications. Soon it could be a reality with the help of synthetic biology. This field of study is already transforming pharmaceuticals and healthcare. According to recent projections, the synthetic biology market is set to reach $37 billion by 2026.1 This article covers all you need to know about this rapidly developing and life-transforming innovation.
What is synthetic biology?
Synthetic biology is the field of science that involves creating new biological systems or organisms by designing and putting together biological components. Scientists use this field to build novel living things. They assemble biological parts like engineers use mechanical parts. This approach allows for custom-made biological solutions, combining engineering principles with life sciences.1 Synthetic biology uses advanced technologies like genome synthesis and assembly, gene editing, and molecular evolution to achieve its goals.2
Key applications in medicine and pharmaceuticals
Engineered cells for cancer treatment
One of the most promising applications of synthetic biology is in cancer treatment. Immune cells, specifically T cells engineered with chimeric antigen receptors (CARs), are revolutionising cancer immunotherapy. These engineered T cells seek for and eliminate malignant cells. For instance, CAR-T therapies like Kymriah and Yescarta have been approved by the FDA and have shown remarkable success in treating leukaemia and lymphoma, achieving complete response rates in many patients.1
Recent advancements also highlight the potential of immune cells called natural killer (NK) cells in immunotherapy. Unlike T cells, NK cells can kill cancer cells without needing specific markers. Scientists can enhance NK cells to make them better cancer fighters, by adding specialised components, similar to the modification made to T cells. These engineered NK cells are safer for patients than modified T cells. They are less likely to cause severe side effects in the body. Additionally, CAR-NK cells offer the possibility of "off-the-shelf" therapies, which can be produced in advance and used as needed without requiring individual customisation.3
Advanced synthetic biology techniques are also enhancing the effectiveness of CAR therapies. Scientists are developing ways to outsmart cancer's evasion tactics. New methods aim to boost immune responses in previously resistant tumours.3 Strategies include developing multi-antigen targeting CARs to prevent tumour cells from evading immune detection and engineering CARs with "on" and "off" switches to control their activity and minimise side effects.3
Furthermore, some common gut bacteria like Salmonella and E. coli can be engineered to fight cancer. These bacteria can either directly attack tumours or stimulate the body's immune defences. This new approach provides an alternative when traditional treatments are ineffective.2
Production of therapeutic chemicals
Synthetic biology facilitates the microbial production of therapeutic chemicals. For instance, engineered yeast can now produce artemisinin, a malaria-fighting drug. This method is more efficient than extracting it from plants. Scientists have modified yeast cells to make this important medicine, offering a sustainable alternative to traditional plant-based production. The new technique ensures a steady, controlled supply of artemisinin. This approach could make the anti-malarial drug more readily available while also increasing yield and reducing costs.1
Diagnosis
Traditional diagnostic methods are often slow and imprecise. The creation of highly specialised and sensitive biosensors has been made possible by cell engineering inspired by synthetic biology. For instance, bacterial sensors can now rapidly detect biomarkers in blood or urine, producing a visible signal when a target molecule is present. This advancement speeds up diagnosis and reduces costs.2
Engineered mammalian cells
Synthetic biology also enables the creation of engineered mammalian cells for various treatments. This approach expands the toolkit for cell-based therapies. It opens up possibilities for personalised medical treatments. HEK-293-β cells, for example, mimic pancreatic beta cells to regulate blood glucose levels in diabetes patients. These cells have shown promise in maintaining glucose homeostasis and correcting diabetic hyperglycemia in mice.1
Additionally, induced pluripotent stem cells (iPSCs) are adult cells reprogrammed to act like embryonic stem cells. Scientists can turn skin or blood cells into these versatile iPSCs. iPSCs can then become any cell type in the body. This process creates personalised cells for treatment without ethical issues. iPSCs avoid controversies linked to using embryonic stem cells. Researchers can produce various cell types from iPSCs for therapy.1
Engineering viruses to fight superbugs
The rise of antimicrobial resistance has created an urgent need for new therapeutic strategies. Synthetic biology provides tools to engineer microbial cells that can fight superbugs. For example, engineered bacteriophages (viruses that infect bacteria) can be designed to target and destroy antibiotic-resistant bacteria. These engineered phages can deliver CRISPR-Cas systems into bacterial cells, specifically targeting and disrupting antibiotic resistance genes.4
Genetic engineering to modify antibiotics
Synthetic biology allows the modification of antibiotic-producing microorganisms to enhance production and diversify the range of antibiotic compounds. For instance, nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) are enzyme complexes that can be engineered to produce novel antibiotics. These enzyme modules can be combined to create new antibiotic classes like glycopeptides and lipopeptides, potentially addressing the growing challenge of drug-resistant infections.4
Infectious diseases
Synthetic biology provides novel strategies to combat infectious diseases. Scientists can redesign bacteria to make compounds that fight harmful pathogens. For instance, researchers have modified Mycoplasma pneumonia bacteria to release enzymes that break down biofilms. Biofilms are protective layers that some harmful bacteria form. This approach shows promise against antibiotic-resistant infections. It offers a new way to fight germs that don't respond to conventional treatments.2
RNA vaccine design with synthetic biology
The promise of RNA-based therapies has been highlighted by the recent success of mRNA COVID-19 vaccinations and the launch of personalised cancer vaccines. Synthetic biology can optimise these RNA-based therapies, improving their efficacy and stability. For instance, synthetic biology can address challenges related to the stability and delivery of mRNA vaccines, showing promise in inducing potent and prolonged immune responses.5
Engineering organoids and tissues
Synthetic biology is also being harnessed to engineer human organoids and tissues. Organoids are 3D structures grown from stem cells that mimic the function of real organs. This technology holds great potential for disease modelling, drug testing, and regenerative medicine.
Creating organoids
Synthetic biology provides new methods to enhance organoid creation. It helps scientists control how cells talk to each other. The field also improves how cells stick together in organoids. These tools allow for better-structured mini-organs in the lab. Researchers can now fine-tune organoid formation more precisely, allowing more accurate 3D models of human organs.6
Applications in regenerative medicine
Organoids have the potential to revolutionise regenerative medicine. In the future, organoids could even be used to grow replacement tissues for transplantation, offering new hope for patients with organ failure.6
Synthetic biology for environmental protection
Synthetic biology is playing an increasingly important role in environmental protection. Engineered organisms can detect and clean up pollutants, offering sustainable solutions to environmental challenges.
Bioremediation using engineered microbes
Bioremediation involves using living organisms to clean up contaminated environments. Engineered microbes can degrade harmful substances such as heavy metals, pesticides, and hydrocarbons. For instance, genetically modified Pseudomonas and Acinetobacter species can break down polycyclic aromatic hydrocarbons (PAHs) in polluted soil. These engineered microbes can enhance the natural degradation processes, making bioremediation more effective.7
Phytoremediation
Phytoremediation involves using plants to remove, degrade, or stabilise pollutants in the environment. Engineered plants can enhance the efficiency of phytoremediation. For example, transgenic tobacco plants expressing bacterial genes can accumulate heavy metals like cadmium and lead, making them effective for cleaning up contaminated soils.7
Artificial intelligence in synthetic biology
AI and machine learning are becoming increasingly integrated into synthetic biology. AI helps design and predict the behaviour of synthetic biological systems, making the engineering process more efficient and precise. For example, AI algorithms can predict protein structures, aiding in the design of new proteins with desired functions.2
Regulatory challenges in synthetic biology
The regulatory landscape for synthetic biology, particularly in Europe, is complex and evolving. Current regulations often struggle to keep up with rapid advances, creating challenges for researchers. European regulations typically distinguish between "contained use" (within laboratories) and "deliberate release" (into the environment). This distinction can create complications for projects that don't fit neatly into either category. For example, a field-use biosensor for arsenic detection in well water encountered regulatory hurdles due to its unclear containment status.8
Future regulations need more adaptability to accommodate novel applications. The concept of "contained release", where field-use products have multiple safety measures, could streamline approvals and foster innovation while ensuring safety. This approach could help bridge the gap between current regulatory categories and the rapidly evolving nature of synthetic biology projects.8
Future prospects and challenges
The future of synthetic biology holds great promise. Advancements in gene editing tools like CRISPR and the development of complex bio-circuits could lead to even more precise and effective therapies. However, the field also faces significant challenges. Ethical considerations, technical hurdles, and safety concerns must be addressed to fully realise the potential of synthetic biology.1
Summary
Synthetic biology is poised to revolutionise medicine and pharmaceuticals. From cancer therapies to diabetes treatments and the efficient production of drugs, the possibilities are vast. As this field continues to evolve, staying informed about its advancements will be crucial. Synthetic biology is not just a scientific endeavour; it's a beacon of hope for a healthier future.
References
- Yan X, Liu X, Zhao C, Chen G-Q. Applications of synthetic biology in medical and pharmaceutical fields. Signal Transduct Target Ther. 2023; 8(1):199.
- Zhang X-E, Liu C, Dai J, Yuan Y, Gao C, Feng Y, et al. Enabling technology and core theory of synthetic biology. Sci China Life Sci. 2023; 66(8):1742–85.
- Clubb JD, Gao TA, Chen YY. Synthetic Biology in the Engineering of CAR-T and CAR-NK Cell Therapies: Facts and Hopes. Clin Cancer Res. 2023; 29(8):1390–402.
- León-Buitimea A, Balderas-Cisneros F de J, Garza-Cárdenas CR, Garza-Cervantes JA, Morones-Ramírez JR. Synthetic Biology Tools for Engineering Microbial Cells to Fight Superbugs. Front Bioeng Biotechnol. 2022; 10:869206.
- Pfeifer BA, Beitelshees M, Hill A, Bassett J, Jones CH. Harnessing synthetic biology for advancing RNA therapeutics and vaccine design. NPJ Syst Biol Appl. 2023; 9(1):60.
- Trentesaux C, Yamada T, Klein OD, Lim WA. Harnessing synthetic biology to engineer organoids and tissues. Cell Stem Cell. 2023; 30(1):10–9.
- Aminian-Dehkordi J, Rahimi S, Golzar-Ahmadi M, Singh A, Lopez J, Ledesma-Amaro R, et al. Synthetic biology tools for environmental protection. Biotechnol Adv. 2023; 68:108239.
- Sundaram LS, Ajioka JW, Molloy JC. Synthetic biology regulation in Europe: containment, release and beyond. Synth Biol (Oxf). 2023; 8(1):ysad009.