Innovation In Synthetic Biology Research Articles

Legal Challenges for Synthetic Biology Innovation

Legal Challenges for Synthetic Biology Innovation

Bayesian and Algebraic Strategies to Design in Synthetic Biology

Innovation in synthetic biology often still depends on large-scale experimental trial and error, domain expertise, and ingenuity. The application of rational design engineering methods promises to make this more efficient, faster, cheaper, and safer. However, this requires mathematical models of cellular systems. For these models, we then have to determine if they can meet our intended target behavior. Here, we develop two complementary approaches that allow us to determine whether a given molecular circuit, represented by a mathematical model, is capable of fulfilling our design objectives. We discuss algebraic methods that are capable of identifying general principles guaranteeing desired behavior; we provide an overview of Bayesian design approaches that allow us to choose a model that has the highest probability of fulfilling our design objectives from a set of models. We discuss their uses in the context of biochemical adaptation and, then, consider how robustness can and should affect our design approach.

Faster, reduced cost calibration method development methods for the analysis of fermentation product using near-infrared spectroscopy (NIRS).

Recent innovations in synthetic biology, fermentation, and process development have decreased time to market by reducing strain construction cycle time and effort. Faster analytical methods are required to keep pace with these innovations, but current methods of measuring fermentation titers often involve manual intervention and are slow, time-consuming, and difficult to scale. Spectroscopic methods like near-infrared (NIR) spectroscopy address this shortcoming; however, NIR methods require calibration model development that is often costly and time-consuming. Here, we introduce two approaches that speed up calibration model development. First, generalized calibration modeling (GCM) or sibling modeling, which reduces calibration modeling time and cost by up to 50% by reducing the number of samples required. Instead of constructing analyte-specific models, GCM combines a reduced number of spectra from several individual analytes to produce a large pool of spectra for a generalized model predicting all analyte levels. Second, randomized multicomponent multivariate modeling (RMMM) reduces modeling time by mixing multiple analytes into one sample matrix and then taking the spectral measurements. Afterward, individual calibration methods are developed for the various components in the mixture. Time saved from the use of RMMM is proportional to the number of components or analytes in the mixture. When combined, the two methods effectively reduce the associated cost and time for calibration model development by a factor of 10.

Redesigning the Genetic Polymers of Life.

Genomes can be viewed as constantly updated memory systems where information propagated in cells is refined over time by natural selection. This process, commonly known as heredity and evolution, has been the sole domain of DNA since the origin of prokaryotes. Now, some 3.5 billion years later, the pendulum of discovery has swung in a new direction, with carefully trained practitioners enabling the replication and evolution of "xeno-nucleic acids" or "XNAs"-synthetic genetic polymers in which the natural sugar found in DNA and RNA has been replaced with a different type of sugar moiety. XNAs have attracted significant attention as new polymers for synthetic biology, biotechnology, and medicine because of their unique physicochemical properties that may include increased biological stability, enhanced chemical stability, altered helical geometry, or even elevated thermodynamics of Watson-Crick base pairing.This Account describes our contribution to the field of synthetic biology, where chemical synthesis and polymerase engineering have allowed my lab and others to extend the concepts of heredity and evolution to synthetic genetic polymers with backbone structures that are distinct from those found in nature. I will begin with a discussion of α-l-threofuranosyl nucleic acid (TNA), a specific type of XNA that was chosen as a model system to represent any XNA system. I will then proceed to discuss advances in organic chemistry that were made to enable the synthesis of gram quantities of TNA phosphoramidites and nucleoside triphosphates, the monomers used for solid-phase and polymerase-mediated TNA synthesis, respectively. Next, I will recount our development of droplet-based optical sorting (DrOPS), a single-cell microfluidic technique that was established to evolve XNA polymerases in the laboratory. This section will conclude with structural insights that have been gained by solving X-ray crystal structures of a laboratory-evolved TNA polymerase and a natural DNA polymerase that functions with general reverse transcriptase activity on XNA templates.The final passage of this Account will examine the role that XNAs have played in synthetic biology by highlighting examples in which engineered polymerases have enabled the evolution of biologically stable affinity reagents (aptamers) and catalysts (XNAzymes) as well as the storage and retrieval of binary information encoded in electronic word and picture file formats. Because these examples provide only a glimpse of what the future may have in store for XNA, I will conclude the Account with my thoughts on how synthetic genetic polymers could help drive new innovations in synthetic biology and molecular medicine.

Responsible innovation in synthetic biology in response to COVID-19: the role of data positionality

Synthetic biology, as an engineering approach to biological systems, has the potential to disruptively innovate the development of vaccines, therapeutics, and diagnostics. Data accessibility and differences in data-usage capabilities are important factors in shaping this innovation landscape. In this paper, the data that underpin synthetic biology responses to the COVID-19 pandemic are analyzed as positional information goods—goods whose value depends on exclusivity. The positionality of biological data impacts the ability to guide innovations toward societally preferred goals. From both an ethical and economic point of view, positionality can lead to suboptimal as well as beneficial situations. When aiming for responsible innovation (i.e. embedding societal deliberation in the innovation process), it is important to consider hurdles and facilitators in data access and use. Central governance and knowledge commons provide routes to mitigate the negative effects of data positionality.

Reflections on the practice of Responsible (Research and) Innovation in synthetic biology

This paper is a critical reflection on the concepts of Responsible Innovation (RI) and Responsible Research and Innovation (RRI). We offer an account of the emergence of these related but different accounts of responsible innovation that have recently been adopted by funders. We further report on our exploration of the knowledge and understanding of these concepts through the views of senior scientists involved in synthetic biology research projects. Though most of our respondents struggled to provide a clear account of RI/RRI we identified that existing “practices of responsibility” include many aspects of RI/RRI but that this often went unrecognized as such. Most respondents associated RI/RRI with risk avoidance. While some visions of RI/RRI see scientists as taking an active role in shaping the future of innovation, we suggest that it is not for such individuals to take decisions alone on the types of futures a society should have available to it.

Future making and responsible governance of innovation in synthetic biology

As partners in a European project for responsible research and innovation (RRI) in synthetic biology, we organized a collaborative and interactive process of real-time technology assessment. This process consisted of two related activities complementing each other as different modes of future making, one focussing on technological options, the other on societal objectives. For the first type of activity, we established a three-year collaboration with the annual international Genetically Engineered Machines competition, stimulating student teams to consider the wider societal ramifications of future options for innovation in synthetic biology. As a follow-up activity in this process of real-time and anticipatory technology assessment, we involved a variety of societal stakeholders and researchers in synthetic biology in workshop dialogues focusing on antibiotic resistance and renewable energy as societal challenges. We invited the participants to critically consider the nature of these challenges and related value-laden issues of concern, and to define in this context opportunities and needs for innovation in synthetic biology. We see both approaches as vital in fulfilling the ambitions of responsible research and innovation. In terms of the governance of innovation, we emphasize the need for a proper toolbox and a co-creation infrastructure as crucial requirements for inclusive, reflexive and responsive practices of future making.

Gene Circuits for Dynamically Regulating Metabolism

Gene circuits are a functional innovation in synthetic biology for engineering cellular behavior. Recent advances have demonstrated that gene circuits can be exploited for dynamically controlling pathway redirection and pathway balance to produce valuable chemicals. The next frontier is to engineer robust, sensitive, and efficient circuits that adapt to changing conditions.

From CBA to Precautionary Appraisal: Practical Responses to Intractable Problems.

The purpose of this essay is to critically review the design of methods for ethically robust forms of technology appraisal in the regulation of research and innovation in synthetic biology. It will focus, in particular, on the extent to which cost-benefit analysis offers a basis for informing decisions about which technological pathways to pursue and which to discourage. A further goal is to consider what (if anything) the precautionary principle might offer in enabling better decisions. And this, in turn, raises questions about why mention of precaution can excite accusations of unscientific bias or irrational, "anti-innovation" extremism. What does the polarized debate tell us about the politics around synthetic biology? In seeking more rigorous, timely, and practical ways to govern these remarkable new technologies, what might we be missing? The sophistication, diversity, and scope of synthetic biology may seem to make it a rather idiosyncratic area for exploring these general issues. It may seem to be a special case, with the bewildering pace of change amplifying the difficulties. But at root, some of the trickiest issues are just specific instances of familiar and long-standing conundrums in the governance of science and technology. The basic challenge is how to weigh up, for a wide range of potential options, the various pros and cons, as viewed from divergent perspectives, and find a way to justify the best course of action on behalf of society as a whole. This is the central problem addressed by a number of techniques in CBA. On the face of it, synthetic biology seems to present just one more application of these well-established and self-confident prescriptive methods. But there do emerge several obstinate, even prohibitive, difficulties for CBA. Although they are well acknowledged by the scholarly literature on and around this topic, they are often sidelined in practice. Yet all are central to the case for applying the concept of precaution to a field like synthetic biology. This essay will briefly explore multicriteria mapping, an appraisal method for exploring contrasting perspectives on emerging technologies, as one practical way to address them. The essay focuses on MCM, not because it presents any sort of panacea for appraisal, but because it is illustrative of the concrete implications of precaution. Setting out even just one among potentially many practical alternative methods at least refutes the last-ditch argument that CBA is the only operational choice.

How to access and exploit natural resources sustainably: petroleum biotechnology.

SummaryAs we transition from fossil fuel reliance to a new energy future, innovative microbial biotechnologies may offer new routes to maximize recovery from conventional and unconventional energy assets; as well as contributing to reduced emission pathways and new technologies for carbon capture and utilization. Here we discuss the role of microbiology in petroleum biotechnologies in relation to addressing UN Sustainable Development Goal 12 (ensure sustainable consumption and production patterns), with a focus on microbially‐mediated energy recovery from unconventionals (heavy oil to methane), shale gas and fracking, bioelectrochemical systems for the production of electricity from fossil fuel resources, and innovations in synthetic biology. Furthermore, using wastes to support a more sustainable approach to fossil fuel extraction processes is considered as we undertake the move towards a more circular global economy.

Detection of chikungunya viral RNA in mosquito bodies on cationic (Q) paper based on innovations in synthetic biology

Chikungunya virus (CHIKV) represents a growing and global concern for public health that needs inexpensive and convenient methods to collect mosquitoes as potential carriers so that they can be preserved, stored and transported for later and/or remote analysis. Reported here is a cellulose-based paper, derivatized with quaternary ammonium groups (“Q-paper”) that meets these needs. In a series of tests, infected mosquito bodies were squashed directly on Q-paper. Aqueous ammonia was then added on the mosquito bodies to release viral RNA that adsorbed on the cationic surface via electrostatic interactions. The samples were then stored (frozen) or transported. For analysis, the CHIKV nucleic acids were eluted from the Q-paper and PCR amplified in a workflow, previously developed, that also exploited two nucleic acid innovations, (“artificially expanded genetic information systems”, AEGIS, and “self-avoiding molecular recognition systems”, SAMRS). The amplicons were then analyzed by a Luminex hybridization assay. This procedure detected CHIKV RNA, if present, in each infected mosquito sample, but not in non-infected counterparts or ddH2O samples washes, with testing one week or ten months after sample collection.

Synthetic DNA Synthesis and Assembly: Putting the Synthetic in Synthetic Biology.

The chemical synthesis of DNA oligonucleotides and their assembly into synthons, genes, circuits, and even entire genomes by gene synthesis methods has become an enabling technology for modern molecular biology and enables the design, build, test, learn, and repeat cycle underpinning innovations in synthetic biology. In this perspective, we briefly review the techniques and technologies that enable the synthesis of DNA oligonucleotides and their assembly into larger DNA constructs with a focus on recent advancements that have sought to reduce synthesis cost and increase sequence fidelity. The development of lower-cost methods to produce high-quality synthetic DNA will allow for the exploration of larger biological hypotheses by lowering the cost of use and help to close the DNA read-write cost gap.

High-throughput multiplexed xMAP Luminex array panel for detection of twenty two medically important mosquito-borne arboviruses based on innovations in synthetic biology

Mosquito-borne arboviruses are emerging world-wide as important human and animal pathogens. This makes assays for their accurate and rapid identification essential for public health, epidemiological, ecological studies. Over the past decade, many mono- and multiplexed assays targeting arboviruses nucleic acids have been reported. None has become established for the routine identification of multiple viruses in a “single tube” setting. With increasing multiplexing, the detection of viral RNAs is complicated by noise, false positives and negatives. In this study, an assay was developed that avoids these problems by combining two new kinds of nucleic acids emerging from the field of synthetic biology. The first is a “self-avoiding molecular recognition system” (SAMRS), which enables high levels of multiplexing. The second is an “artificially expanded genetic information system” (AEGIS), which enables clean PCR amplification in nested PCR formats. A conversion technology was used to place AEGIS component into amplicon, improving their efficiency of hybridization on Luminex beads. When Luminex “liquid microarrays” are exploited for downstream detection, this combination supports single-tube PCR amplification assays that can identify 22 mosquito-borne RNA viruses from the genera Flavivirus, Alphavirus, Orthobunyavirus. The assay differentiates between closely-related viruses, as dengue, West Nile, Japanese encephalitis, and the California serological group. The performance and the sensitivity of the assay were evaluated with dengue viruses and infected mosquitoes; as few as 6–10 dengue virions can be detected in a single mosquito.

The Monster and the polar bears: constructing the future knowledge landscape of synthetic biology to inform responsible innovation

Responsible innovation in synthetic biology requires a research agenda to analyze and assess functional applications and their plausible future impacts on social–ecological systems alongside the many other ‘solutions’ (e.g. technologies, policies, social and behavioural interventions, changes to infrastructure) available to achieve shared goals for a sustainable society. Constructing the future knowledge landscape of synthetic biology could inform anticipation to explore how synthetic biology may redefine human–environment interactions and shape visions, expectations, and fears about the future.

Framing responsible innovation in synthetic biology: the need for a critical discourse analysis approach

Various framings of responsible innovation, some specific to synthetic biology and others more general, have emerged, evoking notions of responsibility in science and innovation. They are represented by a set of narratives that are far from stabilised, being subject to the ongoing debate and contestation. We aim to understand the emergence of discourses of responsible (research and) innovation and dynamics influencing them. This article proposes a critical discourse analysis approach to gain such understanding.

IGEM as laboratory in responsible research and innovation

In this paper, we present two different approaches to responsible research and innovation in synthetic biology. By combining these approaches, we aim to facilitate a process of mutual learning, involving young students involved in the international Genetically Engineered Machines (iGEM) competition, researchers from the field and a variety of societal stakeholders in the governance of synthetic biology innovation.

Participation in iGEM Competition; Education toward Synthetic Biology Innovation

Synthetic biology knowledge has been enhanced around the world through a ´learn by doing´ approach. The iGEM competition is being used as a catalyst to get students involved in molecular biology, mathematics, and physics multidisciplinary research and application. This groundbreaking method has reached its 10th anniversary and is going viral through the academic community. This strategy is transforming science by encouraging creative ideas and innovation in academic research, which could be a major advantage for South America technological development.

Standardization, IPRs and Open Innovation in Synthetic Biology

An effective and just sharing of resources for innovation needs a supportive infrastructure. One such infrastructure of both historic and contemporary significance is the development of standards. Considering recent developments within the software and ICT industries, it seems fair to assume that the process of standardization may also have significant impact on the development and adoption of Synthetic Biology (SB). Within SB different standardization efforts have been made, but few have assumed dominance or authority. Standardization efforts within SB may differ within various technical areas, and also the basic processes of standard creation can be divided into various categories. The different technical areas and processes for standardization differ in their speed, handling of interests and ability to dodge possible IPR concerns. Out of this notion arises i.a. the following questions: How comparable is engineering in SB to more traditional fields of engineering?; What type of standards have emerged and what bearing have IPRs on these?; and, How applicable are the approaches adopted by the standards-setting organizations in the information and communication technology (ICT) to biological standards? These and further legal issues related to IP, regulation, standardization, competition law & open innovation require a careful consideration of new user-generated models and solutions. Before this background, our paper seeks to describe IP and standardization aspects of SB in order to discuss them in the context of the “open innovation” discourse. We concentrate on describing the technology and identifying areas of particular relevance. Ultimately we also sketch out open questions and potential solutions requiring further research. However, due to the limitation of this paper we do not aim to create elaborated theories or to propose solutions in more detail. Rather this paper, which will be complemented by more extensive follow-up studies, provides a first overview on the complex questions that we are currently dealing with. To achieve this modest goal, section 1 commences with a brief introduction to the fascinating science of SB and a description of recent technological advances and applications. This will lead us to section 2, in which we will address standard setting efforts in SB, as well as the relevance and governance of various IPRs for specific SB standards. This provides the basis for section 3, in which we debate problematic issues and summarize our conclusions.

Complex Adaptive Systems Drive Innovations in Synthetic Biology

The resultant outcome of synthetic biology research offers the promise of changing the way that we create energy, produce food, optimize industrial processing, and detect, prevent, and cure diseases. Researchers can now realize the significant benefits of the cloud computing model to reduce IT cost and complexity, enhance R&D collaboration, and improve bioinformatics to allow lifesciences organizations to focus on answering some of lifes most challenging questions.

A survey of enabling technologies in synthetic biology.

BackgroundRealizing constructive applications of synthetic biology requires continued development of enabling technologies as well as policies and practices to ensure these technologies remain accessible for research. Broadly defined, enabling technologies for synthetic biology include any reagent or method that, alone or in combination with associated technologies, provides the means to generate any new research tool or application. Because applications of synthetic biology likely will embody multiple patented inventions, it will be important to create structures for managing intellectual property rights that best promote continued innovation. Monitoring the enabling technologies of synthetic biology will facilitate the systematic investigation of property rights coupled to these technologies and help shape policies and practices that impact the use, regulation, patenting, and licensing of these technologies.ResultsWe conducted a survey among a self-identifying community of practitioners engaged in synthetic biology research to obtain their opinions and experiences with technologies that support the engineering of biological systems. Technologies widely used and considered enabling by survey participants included public and private registries of biological parts, standard methods for physical assembly of DNA constructs, genomic databases, software tools for search, alignment, analysis, and editing of DNA sequences, and commercial services for DNA synthesis and sequencing. Standards and methods supporting measurement, functional composition, and data exchange were less widely used though still considered enabling by a subset of survey participants.ConclusionsThe set of enabling technologies compiled from this survey provide insight into the many and varied technologies that support innovation in synthetic biology. Many of these technologies are widely accessible for use, either by virtue of being in the public domain or through legal tools such as non-exclusive licensing. Access to some patent protected technologies is less clear and use of these technologies may be subject to restrictions imposed by material transfer agreements or other contract terms. We expect the technologies considered enabling for synthetic biology to change as the field advances. By monitoring the enabling technologies of synthetic biology and addressing the policies and practices that impact their development and use, our hope is that the field will be better able to realize its full potential.