SynBio, Volume 3, Issue 3 (September 2025) – 5 articles

Metabolic engineering of mesenchymal stem/stromal cells (MSCs) represents a compelling frontier for advanced cellular therapies, enabling the precise tuning of their biological outputs. This feature paper examines the critical role of engineered culture microenvironments, specifically 3D platforms, hypoxic preconditioning, and other priming approaches, which are synthetic biology strategies used to guide and optimize MSC metabolic states for desired functional outcomes. We show that these non-genetic approaches can significantly enhance MSC survival, immunomodulatory capacity, and regenerative potential by shifting their metabolism toward a more glycolytic phenotype. Furthermore, we propose a new paradigm of “designer” MSCs, which are programmed with synthetic circuits to sense and respond to the physiological cues of an injured microenvironment. This approach promises to transform regenerative medicine from an inconsistent field into a precise, predictable, and highly effective therapeutic discipline. Full article

Silicon has a striking similarity to carbon and is found in plant cells. However, there is no specific role that has been assigned to silicon in the life cycle of plants. The amount of silicon in plant cells is species specific and can reach levels comparable to macronutrients. Silicon is used extensively in artificial intelligence, nanotechnology, and the digital revolution, and thus can serve as an informational molecule such as nucleic acids. The diverse potential of silicon to bond with different chemical species is analogous to carbon; thus, it can serve as a structural candidate similar to proteins. The discovery of large amounts of silicon on Mars and the moon, along with the recent development of enzyme that can incorporate silicon into organic molecules, has propelled the theory of creating silicon-based life. The bacterial cytochrome has been modified through directed evolution such that it could cleave silicon–carbon bonds in organo-silicon compounds. This consolidates the idea of utilizing silicon in biomolecules. In this article, the potential of silicon-based life forms has been hypothesized, along with the reasoning that autotrophic virus-like particles could be used to investigate such potential. Such investigations in the field of synthetic biology and astrobiology will have corollary benefits for Earth in the areas of medicine, sustainable agriculture, and environmental sustainability. Full article

Stem cells, unspecialized cells with regenerative and differentiation capabilities, hold immense potential in regenerative medicine, exemplified by hematopoietic stem cell transplantation. However, their clinical application faces significant limitations, including their tumorigenic risk due to uncontrolled proliferation and cellular heterogeneity. This review explores how synthetic biology, an interdisciplinary approach combining engineering and biology, offers promising solutions to these challenges. It discusses the concepts, toolkit, and advantages of synthetic biology, focusing on the design and integration of genetic circuits to program stem cell differentiation and engineer safety mechanisms like inducible suicide switches. This review comprehensively examines recent advancements in synthetic biology applications for stem cell engineering, including programmable differentiation circuits, cell reprogramming strategies, and therapeutic cell engineering approaches. We highlight specific examples of genetic circuits that have been successfully implemented in various stem cell types, from embryonic stem cells to induced pluripotent stem cells, demonstrating their potential for clinical translation. Despite these advancements, the integration of synthetic biology with mammalian cells remains complex, necessitating further research, standardized datasets, open access repositories, and interdisciplinary collaborations to build a robust framework for predicting and managing this complexity. Full article

Cell-free protein synthesis (CFPS) has transformed protein production capabilities by eliminating cellular constraints, enabling the rapid expression of difficult-to-produce proteins in an open, customizable environment. As CFPS applications expand from fundamental research to industrial production, therapeutic manufacturing, and point-of-care diagnostics, the diverse array of reactor formats has become increasingly important yet challenging to navigate. This review examines the evolution and characteristics of thirteen major CFPS reactor formats, from traditional batch systems to advanced platforms. The historical development of CFPS reactors from the 1960s to present day is presented. Additionally, for each format, operational principles, advantages, limitations, and notable applications are evaluated. The review concludes with a comparative assessment of reactor performance across critical parameters, including productivity, scalability, technical complexity, environmental stability, and application suitability. To our knowledge this structured analysis is the first to focus predominantly on the various reactor formats of cell-free systems and to provide a guide to assist researchers in choosing the reactor type that best fits their specific applications. Full article

Synthetic biology (SynBio) is an emerging interdisciplinary field that applies engineering principles to the design and construction of novel biological systems or the redesign of existing natural systems for new functions. As autotrophs with complex cellular architectures, plants possess inherent capabilities to serve as “living factories” for SynBio applications. Recent advancements in genetic engineering, genome editing, and transformation techniques are improving the precision and programmability of plant systems. Innovations, such as CRISPR systems, prime editing strategies, and in planta and nanoparticle-mediated delivery, are expanding the SynBio toolkit for plants. However, the efficient delivery of genetic constructs remains a barrier due to plant systems’ complexity. To address these limitations, SynBio is increasingly integrating iterative Design–Build–Test–Learn (DBTL) cycles, standardization, modular DNA assembly systems, and plant-optimized toolkits to enable predictable trait engineering. This review explores the technological foundations of plant SynBio, including genome editing and transformation methods, and examines their integration into engineered systems. Applications, such as biofuel production, pharmaceutical biosynthesis, and agricultural innovation, are highlighted, along with their ethical, technical, and regulatory challenges. Ultimately, SynBio could offer a transformative path toward sustainable solutions, provided it continues to align technological advances with public interest and global sustainability goals. Full article