Exploring presentations of sustainability by US synthetic biology companies

Karabin, James; Mansfield, Izaac; Frow, Emma

doi:10.1371/journal.pone.0257327

Cited by 5 publications

(2 citation statements)

References 36 publications

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“…Despite the aforementioned challenges, Synthetic Biology is rapidly transitioning from laboratory experiments to tangible, real-world applications [104][105][106] . In 2019, ZBiotics Company, USA, pioneered this field by being the first to produce and sell genetically engineered probiotic products, marking the beginning of a burgeoning industry.…”

Section: Relationship Between Nanobody Production and Tnfα Concentrat...mentioning

confidence: 99%

Engineering a novel probiotic toolkit inEscherichia coli Nissle1917for sensing and mitigating gut inflammatory diseases

Weibel,

Curcio,

Schreiber

et al. 2024

Preprint

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Inflammatory Bowel Disease (IBD) is characterized by chronic intestinal inflammation with no cure and limited treatment options that often have systemic side effects. In this study, we developed a target-specific system to potentially treat IBD by engineering the probiotic bacteriumEscherichia coli Nissle 1917(EcN). Our modular system comprises three components: a transcription factor-based sensor (NorR) capable of detecting the inflammation biomarker nitric oxide, a type 1 hemolysin secretion system, and a therapeutic cargo consisting of a library of humanized anti-TNFα nanobodies. Despite a reduction in sensitivity, our system demonstrated a concentration-dependent response to nitric oxide, successfully secreting functional nanobodies with binding affinities comparable to the commonly used drug Adalimumab, as confirmed by ELISA and in vitro assays. This newly validated nanobody library expands EcN therapeutic capabilities. The adopted secretion system, also characterized for the first time in EcN, can be further adapted as a platform for screening and purifying proteins of interest. Additionally, we provided a mathematical framework to assess critical parameters in engineering probiotic systems, including the production and diffusion of relevant molecules, bacterial colonization rates, and particle interactions. This integrated approach expands the synthetic biology toolbox for EcN-based therapies, providing novel parts, circuits, and a model for tunable responses at inflammatory hotspots.Graphical abstractGraphical Table of Contents.The engineered probiotic system: Inflamed intestinal cells release the inflammatory regulator TNFα (depicted as red squares), which promotes inflammation through a positive feedback loop. Concurrently, these cells produce large amounts of nitric oxide (NO, represented by yellow circles) during inflammation. Our custom-engineered EcN biosensor can detect NO using a NorR-based sensor (in purple) and subsequently trigger the production of nanobodies (in turquoise). These nanobodies are then released into the extracellular environment via a specially engineered secretion system in the bacterial host (shown in dark blue). Once outside the cell, the nanobodies attach to TNFα, effectively sequestering them and reducing inflammation. The graph at the bottom of this panel illustrates the general behavior of our system: nanobody production starts upon reaching a certain NO concentration threshold and continues in an NO-dependent fashion. As nanobodies are produced, they capture TNFα, leading to a reduction in inflammation and a decrease in NO production. This decrease in NO then halts the nanobody production.SignificanceProbiotics can be engineered to detect and act upon extracellular disease indicators, optimizing therapeutic outcomes. Particularly, self-regulating sense-and-respond genetic circuits have the potential to enhance the accuracy, efficacy, and adaptability of treatment interventions. In this study, we developed and characterized a new integrated and modular toolkit that detects a gut inflammation biomarker, specifically nitric oxide, and responds to it in an inducible manner by secreting humanized nanobodies targeting the pro-inflammatory molecule TNFα. We also develop a coarse-grained mathematical framework for modelling engineered probiotic activity in the gut. This novel system contributes to current efforts to develop new engineered probiotic systems and holds promise for inspiring new treatments for gut inflammation associated with various autoimmune diseases.

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Section: Relationship Between Nanobody Production and Tnfα Concentrat...mentioning

confidence: 99%

Engineering a novel probiotic toolkit inEscherichia coli Nissle1917for sensing and mitigating gut inflammatory diseases

Weibel,

Curcio,

Schreiber

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Synthetic biology is oriented to designing bio-based industrial applications, hence its focus on engineering efficient solutions. However, these solutions are often framed in terms of technological drop-in replacement of commodities or substitutions for petrochemical equivalents (Ginsberg & Chieza, 2018;Karabin et al, 2021). This limits the envisioned bio-based future to the replacement of non-renewable chemical production sources with renewable ones.…”

Section: Bio-based Futurementioning

confidence: 99%

Metabolism Instead of Machine: Towards an Ontology of Hybrids

2022

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The emerging field of synthetic biology aims to engineer novel biological entities. The envisioned future bio-based economy builds largely on “cell factories”: organisms that have been metabolically engineered to sustainably produce substances for human ends. In this paper, we argue that synthetic biology’s goal of creating efficient production vessels for industrial applications implies a set of ontological assumptions according to which living organisms are machines. Traditionally, a machine is understood as a technological, isolated and controllable production unit consisting of parts. But modified organisms, or hybrids, require us to think beyond the machine paradigm and its associated dichotomies between artificial and natural, organisms and artefacts. We ask: How may we conceptualise hybrids beyond limiting ontological categories? Our main claim is that the hybrids created by synthetic biology should be considered not as machines but as metabolic systems. We shall show how the philosophical account of metabolism can inform an ontology of hybrids that moves beyond what we call the “machine ontology”, considering that metabolism enables thinking beyond the dominant dichotomies and allows us to understand and design lifeforms in a bio-based economy. Thus, the aim of this paper is twofold: first, to develop the philosophical ontology of hybrids, and second, to move synthetic biology beyond the problematically limiting view of hybrids.

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The logic of carbon substitution: from fossilised life to “cell factories”

Ehrenstein,

Rudge

2024

Rev Agric Food Environ Stud

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This paper examines how researchers in biotechnology reflect on the challenges of turning microbes into what they call “cell factories”. These researchers use the tools of genome editing to harness the biochemistry of single cell organisms, such as bacteria, yeasts and microalgae, and tweak the enzymatic reactions of their metabolism. One research priority is to engineer microbes able to feed on agricultural residues and assemble drop-in compounds to be used in a range of commercial products, from drugs and food additives, to cosmetics, detergents and fuels. To justify financial support for such research, arguments about the need to move away from petroleum as a source of energy and feedstock for chemical synthesis are put forward, underpinned by concerns for climate change, resource renewability and energy security. Drawing on interviews with scientists, we explore what it means for them to make “cell factories” and discuss how they problematise the logic of carbon substitution that orientates their work. Biotechnology is expected to support a shift from one source of carbon, past life gone through slow geological cycles, to a different source of carbon, renewable biomass metabolised by living microbes. As scientists face unhappy cells, recalcitrant plant fibres and unfair competition from fossil-based processes, the promise of carbon substitution tends to be most convincing in the confined space of the lab where faith in biotechnology goes hand in hand with a pragmatic commitment to sustainability. We speculate that the researchers might be failed by the system that biotechnology seeks to (partially) replace, the conditions of which are shaped not around the material constraints of making “cell factories”, but around fossilised life cracked in ever-greater quantities.

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Exploring presentations of sustainability by US synthetic biology companies

Cited by 5 publications

References 36 publications

Engineering a novel probiotic toolkit inEscherichia coli Nissle1917for sensing and mitigating gut inflammatory diseases

Engineering a novel probiotic toolkit inEscherichia coli Nissle1917for sensing and mitigating gut inflammatory diseases

Metabolism Instead of Machine: Towards an Ontology of Hybrids

The logic of carbon substitution: from fossilised life to “cell factories”

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