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Science
14 July 2024

How Synthetic Biology Is Breaking Out Of The Lab

From space missions to remote healthcare, synthetic biology is tackling challenges beyond the lab, transforming how we produce medicines, monitor environments, and promote health.

Imagine a world where medicines, vital chemicals, and even therapeutic bacteria can be produced on-demand, wherever and whenever they are needed. This is not a scene from a science fiction novel, but a promising shift in biotechnology that researchers are actively developing today. Synthetic biology, an interdisciplinary branch that combines biology and engineering, is moving beyond the confines of the lab to tackle global challenges in resource-poor settings, space missions, and other demanding environments.

Synthetic biology holds tremendous potential for addressing some of the most pressing global needs. From sustainable development to healthcare, the ability to engineer biological systems has ramifications across various sectors. One of the most immediate applications is in bioproduction, where microorganisms are transformed into mini-factories that churn out valuable products. However, the transition of synthetic biology innovations from controlled laboratory settings to variable and often harsh real-world conditions is fraught with challenges. Researchers Sierra M. Brooks and Hal S. Alper have delved into these issues in their comprehensive study, highlighting the hurdles and envisioning a future where synthetic biology operates autonomously outside the traditional lab environment.

Deploying synthetic biology beyond the lab environment can be categorized into three main areas: bioproduction, biosensing, and closed-loop therapeutic and probiotic delivery. Each of these areas presents unique challenges that require innovative solutions, making the field a dynamic and exciting one to watch.

Bioproduction is perhaps the most mature application, where microorganisms are engineered to produce everything from pharmaceuticals to biofuels. This ability to turn microbes into producers of valuable chemicals is not new, but scaling this to outside-the-lab environments is where the true potential lies. Take, for example, the use of synthetic biology in remote military missions and space explorations. Current research efforts, including those backed by the Defense Advanced Research Projects Agency (DARPA) and NASA's Translational Research Institute for Space Health (TRISH), are aimed at developing systems that can produce needed medicines and materials on-demand, without the cold chain logistics typically required for drug storage and transport

Cell-free systems offer a fascinating solution to some of these challenges. Instead of relying on living cells that may deteriorate under harsh conditions, cell-free platforms use the molecular machinery of cells in an open environment. This can be particularly advantageous for missions in extreme conditions, like space. "Cell-free platforms bypass the need for viable cells, facilitating the manipulation of metabolism, transcription, and translation through the exogenous addition of non-native substrates," the researchers note.

In addition to bioproduction, advancements in synthetic biology are paving the way for innovative biosensing technologies. These biosensors can detect various biomarkers and environmental hazards in real-time, making them invaluable tools for medical diagnostics and environmental monitoring. Imagine a biosensor that can be sprayed over a field to detect pesticide levels or deployed on a spacecraft to monitor astronaut health. These applications are not just theoretical; research is actively developing such platforms, integrating them with modern technologies for real-time data analysis and decision-making.

One of the more compelling aspects of synthetic biology in biosensing is its potential to aid developing countries. Poor resource settings often lack the infrastructure for sophisticated diagnostic tools. However, robust and portable biosensors could offer real-time information on water quality, pathogen presence, and even food safety. "The use of synthetic biosensors for hazard detection is especially prevalent in developing nations for the detection of hazards and contaminants such as pathogens, chemical contaminants, and harmful bacteria," the study points out.

The third key area where synthetic biology is making waves is in closed-loop therapeutic and probiotic delivery systems. These systems combine biosensing and therapeutic delivery into an autonomous cycle that can offer consistent and responsive treatments. For instance, engineered microbes might detect a pathogenic infection in the body and subsequently produce and deliver the appropriate therapeutic compound. This approach could revolutionize healthcare by providing treatments in real-time without the need for constant medical supervision. It's particularly impactful for remote or underserved areas where access to healthcare is limited.

An excellent example of this innovative approach is the work done on Pseudomonas aeruginosa, a multi-drug-resistant pathogen. Researchers have engineered E. coli Nissle 1917 to sense the pathogen and release a toxin specifically targeting it. This system was shown to clear Pseudomonas infections effectively in mouse models, pointing the way toward similar treatments for human infections.

Despite these advancements, there are significant challenges to deploying synthetic biology platforms outside the controlled environment of a laboratory. One such challenge is ensuring long-term stability. Biological systems are inherently sensitive to environmental conditions, and maintaining their functionality over extended periods is difficult. For instance, while spores of Bacillus subtilis are incredibly resilient, even over centuries, ensuring the metabolic activity of engineered microbes remains consistent is another significant hurdle researchers are tackling.

Another challenge is minimizing the requirement for specialized equipment and expertise to operate these systems. Efforts are being made to integrate synthetic biology with user-friendly, portable technologies such as microfluidic devices, wearable hydrogels, and ingestible capsules. These platforms could potentially be monitored and controlled using smartphone apps, reducing the need for trained personnel.

To mitigate some of these challenges, researchers are turning to innovative solutions like the encapsulation of microbes. For instance, engineered microbes could be encapsulated in hydrogels to maintain their viability and functionality over extended periods. This method ensures that the microbes are protected from harsh environmental conditions while still being able to perform their intended functions, such as producing a therapeutic compound or sensing a specific analyte.

The potential applications of synthetic biology outside the lab are vast and varied. In terms of agriculture, synthetic biology could revolutionize the way we approach crop production and pest control. Plant-growth-promoting rhizobacteria (PGPR) that are engineered to enhance crop yields and resist pests could be delivered via aerial spraying, much like crop dusting today. This approach is not only environmentally friendly but also reduces the reliance on chemical fertilizers and pesticides, making farming more sustainable.

Synthetic biology even holds promise for space exploration. Imagine future Mars missions where astronauts use engineered microbes to produce essential compounds on-demand, reducing the need to carry vast amounts of supplies from Earth. This concept of "terraforming" Mars, using synthetic biology to create a habitable environment, is not as far-fetched as it sounds. Researchers are studying extremophiles, organisms that can survive in extreme conditions, to understand better how life might be sustained on other planets.

The promise of synthetic biology in these far-flung applications is tempered by the realities of current technological and biological limitations. Significant investments in research and development are necessary to overcome these barriers. As the authors of the study note, "Multidisciplinary developments in synthetic biology, materials science, electrical engineering, and other related disciplines are essential for enabling outside-the-lab applications."

A critical aspect of future research will be ensuring the biosafety and biosecurity of these engineered systems. Horizontal gene transfer, where genetic material is transferred between organisms, poses a particular risk. Ensuring that engineered microbes do not inadvertently spread their modified genes to other organisms is crucial. Researchers are developing biocontainment strategies to address these concerns, including using bacterial species that require specific nutrients not found in nature, preventing them from surviving outside controlled environments.

The future of synthetic biology is undoubtedly exciting. As the field continues to advance, the possibilities for its applications expand. Whether it's producing vital medications on-demand during space missions or providing real-time biosensing in remote areas, the potential impact of synthetic biology on our world is immense. As we continue to push the boundaries of what is possible, we must also remain mindful of the ethical and safety implications of deploying these powerful technologies in the real world.

In the words of the study's authors, "Synthetic biology is undergoing a shift in paradigm from utilizing biology to deploying biology." This transformation holds the key to addressing some of the most pressing challenges facing our world today and promises a future where biological engineering can be harnessed for the greater good.

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