Engineered bacteriophages (phages) are emerging as a promising next generation of antibacterial phage therapeutics, facilitated by advances in synthetic biology, genome engineering, and computational design. Engineered phage therapeutics offer standardised genome designs, expanded functionality, and improved manufacturability, which could potentially help to overcome regulatory barriers. However, genetically engineered phages raise additional biosafety and environmental concerns, making the development of effective biocontainment strategies important for clinical use. Here, we review current approaches for phage genome engineering, alongside the evolving regulatory frameworks for engineered phages. We evaluate emerging biocontainment strategies for therapeutic phages and propose a framework for assessing trade-offs between biocontainment stringency, evolutionary robustness against escape mutants, therapeutic efficacy, and translational feasibility.

Hair cosmetics are undergoing a transition from conventional formulations based on passive surface deposition toward biotechnology-driven systems designed to interact with hair and scalp at the molecular level. Recent advances in proteins, peptides, biobased polymers, and responsive delivery platforms are enabling targeted repair of keratin damage, controlled reshaping, durable protection, and modulation of follicular activity. These technologies exploit biological specificity, renewable feedstocks, and programmable material properties to address limitations associated with traditional petrochemical ingredients. In this review, we examine how biotechnology is emerging as a unifying platform for hair cosmetic science, integrating biomolecular engineering, smart materials, computational design, and artificial intelligence to create more effective, sustainable, and biologically inspired hair-care solutions.

Organoids and engineered tissues have emerged as powerful models of human biology, yet their development and function are often characterized through endpoint measurements that provide only static snapshots of dynamic biological processes. Recent advances in stretchable mesh electronics, developmental biointegration, and organoid engineering have enabled the creation of cyborg tissues with embedded sensing, stimulation, and computational capabilities. This review highlights recent progress in developmental bioelectronic integration, multifunctional tissue mapping, biological state reconstruction, and artificial intelligence (AI)-enabled cyborg systems. We discuss how embedded bioelectronics can be combined with molecular and spatial profiling technologies to characterize tissue function, developmental trajectories, and biological states. These advances establish cyborg tissues as biologically integrated platforms for regenerative medicine, disease modeling, drug discovery, and adaptive biotechnology.

Jankowska, Katneni, Lin and colleagues demonstrate that synonymous recoding of therapeutic protein a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 is not functionally neutral as it reshapes proteostasis, glycosylation, and catalytic activity in expression system-dependent ways, revealing that gene sequence design and manufacturing platform form an integrated determinant of therapeutic protein quality.

Incorporating unnatural amino acids (uAAs) programs protein polymers to undergo multistep shape shifting between distinct nanostructures. uAA chemistry and position determine nanostructure morphology and temperature-dependent morphological transitions, while photoswitchable uAAs enable reversible light-driven shape shifting that alters cargo encapsulation and enzymatic activity, opening new possibilities for designing adaptive protein materials.

Sun et al. engineer Saccharomyces cerevisiae to convert glucose into indole-3-acetonitrile and multiple downstream tryptophan-derived indole compounds. By combining cytochrome P450 engineering with cofactor, endoplasmic reticulum, and precursor-supply and enzyme-mining strategies, they establish an artificial route toward 3,3′-diindolylmethane production and demonstrate the IAN as a branch point for expanding yeast biosynthesis.

mRNA therapeutics have emerged as a transformative platform for vaccines and protein replacement therapies, yet their broader clinical and commercial translation remains constrained by challenges in product stability, safety, potency, and delivery efficiency. This review provides a comprehensive overview of the current state of mRNA therapeutic development across the entire product lifecycle, spanning RNA design, manufacturing process optimization and characterization, scale-up and continuous manufacturing, lipid nanoparticle design, formulation, and delivery. Unlike prior reviews that focus on individual stages, we present an end-to-end perspective linking drug substance and drug product development, with emphasis on technological advances over the past 5 years. By integrating these advances, this review offers a practical roadmap for overcoming key bottlenecks and accelerating next-generation mRNA therapeutics.

We report a single, fully genome-engineered Pseudomonas putida ETAB-HB V4 strain for valorizing complex plastic-derived feedstocks into (R)-3-hydroxybutyrate. The results support open-loop recycling strategies for converting plastic waste into value-added products.

Autoimmune diseases (ADs) are characterized by persistent immune dysregulation and oxidative imbalance, yet current therapies largely rely on broad immunosuppression that rarely restores durable immune homeostasis. Growing evidence indicates that reactive oxygen species (ROS) function as both inflammatory mediators and essential immune regulators, limiting the effectiveness of indiscriminate ROS scavenging. Here, we highlight nanozymes as emerging catalytic therapeutics for (ADs) and redefine their role as regulators of redox-guided immune homeostasis. We propose a catalytic redox set-point framework in which nanozymes restore a physiological redox window that supports immune regulation while constraining pathological inflammation. This perspective establishes a unifying mechanistic link between nanozyme catalysis and immune restoration, and outlines future opportunities for tolerance-oriented design and clinical translation.

Plasmids are central tools in biotechnology, yet their copy number is often treated as fixed. This study shows that plasmid copy number can be dynamically controlled to tune gene expression, growth, stability, and DNA transfer across bacterial hosts, expanding the flexibility and predictability of engineered biological systems.

Debates about whether organoid intelligence systems are conscious, or can suffer, often stall on the question of what these organoid entities and systems are. A reflexive, anticipatory, and deliberative approach, grounded in a moral principle of complexity, instead asks what they do and provides guidance on that basis. Unanswerable questions are transformed into more workable processes.

When replacing expensive redox cofactors, making biomimetic cofactors with desirable thermostability and redox properties is only half of the equation; enzymes must also be able to use them. Ji and colleagues confront that trade-off by pairing the development of a thermostable carbocyclic cofactor with a dedicated regeneration enzyme for sustained biocatalysis.

Cellular agriculture uses cells to produce animal-derived products without raising whole animals. However, scaling cultivated meat into affordable, structured food remains difficult. In this opinion, we argue that this difficulty reflects not isolated technical gaps but constraint coupling: the interdependence of tissue thickness, vascularization, cell-state stability, media cost, bioreactor scale, food safety, and consumer acceptance within the product goal of food-grade meat. We interpret recent diversification through this framework. Nonfood tissues and low-complexity cell-derived products do not eliminate these constraints but reconfigure them around product-specific requirements, including ingredient identity, material performance, durability, regulatory context, and commercial feasibility. This reframing positions diversification beyond meat as product-specific pathways with distinct constraint profiles.

Glioblastoma remains highly aggressive, with limited treatment response and poor prognosis. Tissue biopsy (TB) is invasive and fail to capture tumor heterogeneity or temporal dynamics. Liquid biopsy (LB) provides a noninvasive alternative for real-time monitoring via circulating biomarkers, including cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) in plasma, cerebrospinal fluid (CSF), urine, and saliva. This review advances beyond prior biomarker catalogs by delivering a quantitative technology scorecard comparing cfDNA-, CTC-, and EV-based platforms in terms of sensitivity, clinical actionability, cost, and scalability. We introduce a multimodal decision matrix and an artificial intelligence (AI)-driven fusion pipeline integrating fragmentomics, EV proteomics, and CTC transcriptomics to enhance minimal residual disease detection and guide precision neuro-oncology.

5-Aminolevulinic acid (5-ALA), a nonproteinogenic amino acid, has emerged as a versatile metabolite for applications in health, agriculture, and sustainability. Advances in ALA synthase engineering and metabolic rewiring have enabled scalable biosynthesis. The next frontier should expand beyond production, positioning it as a gateway to future biotechnological applications.

Li et al. develop a carbohydrate-tagged DNA oligonucleotide that binds the shared scaffold of Streptococcus pyogenes Cas9 guide RNAs. One inhibitor suppresses editing driven by multiple guides, while carbohydrate tags improve stability and preferentially enhance activity in selected cell models. Endogenous editing is confirmed in human cells and normal liver organoids.

Qi et al. develop DipTRANS (Direct in planta Transformation), a soil-based transformation platform that entirely bypasses plant tissue culture. By integrating developmental regulator-induced regeneration, cutting propagation, and viral delivery, DipTRANS enables rapid heritable transformation, programmable transgene removal and activation, and iterative, transgene-free genome engineering in Nicotiana benthamiana.

The ability to adjust therapeutic protein output in engineered probiotics would improve the efficacy and safety of probiotics for the treatment of many diseases. We engineered a combinatorial secretion construct library in Saccharomyces cerevisiae var. boulardii to enable an improved expression and secretion range of both reporter and therapeutic proteins.

Holtz et al. repurpose RamR, a bacterial protein implicated in antibiotic resistance, into biosensors for plant-derived anticancer, antimalarial, and analgesic alkaloids. In yeast, these sensors convert alkaloid levels into a fluorescent readout, replacing slow and costly chemical analysis. This readout identifies mitochondrial function and lipid metabolism as unexpected engineering targets.

Microbial electrochemical technologies (METs) are emerging with innovative applications in various fields by harnessing the combined action of electrodes and microbes. What if METs could be the key to circularity in wastewater treatment? What if METs could be employed to convert electricity and CO2, or waste, into valuable organics? What if new bioinspired materials could be produced through METs? What if METs could be used as smart bio-based sensors? We provide our vision for the future of METs in four sectors: water treatment, industrial biotechnology, electronics, and biosensors. We showcase why and how METs could advance or replace state-of-the-art technologies and discuss the challenges that must be overcome to make METs part of an electrified future powered by microbes.

In their work, Windisch et al. demonstrate the successful adaptation of volumetric 3D printing to photosynthetically active green microalgae-based engineered living materials (ELMs), addressing key fabrication challenges associated with light scattering and absorption in cell-laden materials. Their work expands the fabrication toolbox for geometrically complex ELMs and highlights volumetric printing as a promising approach for developing functional photosynthetic living materials.

Suh et al. program antigen-poor chondrosarcoma cells to become visible to T cells. Their genetic circuit switches on a T cell-recruiting surface protein only when two chondrosarcoma-selective promoters are active together, while blocking macrophage migration inhibitory factor sustains immunity and drives regression of treated and distant untreated tumors in humanized mice.

Cell therapies are increasingly manufactured in closed, automated culture systems, yet decisions about cell quality, safety, and release still rely largely on sparsely executed, destructive, and offline assays. Over the past 5 years, significant progress has been made in developing biosensors capable of real-time measurement of key biochemical and physicochemical indicators including metabolites, ionic species, and protein-associated stress indicators within cell culture environments. However, most systems remain disconnected from manufacturing workflows and fail to support actionable process control. This opinion article discusses the next phase of innovation and the need to reposition biosensors as process analytical technology, shifting the field from descriptive monitoring toward integrated, decision-driven control of cell therapy manufacturing.

I welcome the discussion raised by Hernández-Huerta and colleagues. While legal provisions regulating the transfer of biological materials are significant, genomic governance goes beyond mere legal compliance. It encompasses transparency, accountability, benefit-sharing, and long-term stewardship. Recent international recommendations emphasize the need for comprehensive governance frameworks for national genomic initiatives.

3D bioprinting has the potential to provide nonanimal alternatives to preclinical testing and revolutionize current clinical and transplantation practices. Realizing this potential requires a concerted effort to develop and advance European standards and regulatory frameworks, ensuring a clear and safe pathway for the clinical integration of 3D bioprinting.

Epigenetic editing enables programmable and potentially reversible regulation of chromatin states without altering DNA sequences. By establishing a framework of programmable chromatin engineering, epigenetic editing provides new opportunities for designing climate-resilient crops and advancing next-generation precision breeding.

Calls for public engagement in biotechnology governance are ubiquitous but imprecise, leaving practitioners without actionable guidance and allowing institutions to claim engagement benefits without delivering them. We introduce a precision public engagement framework spanning seven dimensions, making choices explicit, enabling accountability, and closing the gap between engagement and legitimacy.

Musculoskeletal (MSK) disorders remain a leading cause of disability, yet effective disease-modifying therapies are limited by poor translational relevance of conventional models. Organ-on-chip (OoC) technologies have emerged as promising platforms for disease modeling and therapeutic discovery. This review highlights recent advances in patient-derived and induced pluripotent stem cell-based OoC systems, multicellular tissue engineering, biomechanical and immune integration, real-time sensing, and data-driven analytics that enhance physiological relevance and predictive capability. We further discuss automated high-throughput screening and machine learning approaches for scalable drug testing and personalized therapeutic prediction. Finally, we address challenges including reproducibility, vascularization, and standardization, and outline a future roadmap toward precision medicine through intelligent OoC platforms and patient-specific digital twins.

New approach methodologies are not a separate market or scientific category, but a heterogeneous set of methodologies whose relevance depends on a clearly defined context of use (CoU). The early definition of CoU should guide validation, qualification, and evidence generation to accelerate regulatory adoption across the EU.

Promoter macro-heterogeneity creates distinct subpopulations that limit bioproduction. Combining flow cytometry, scRNA-seq-based modelling, and single-cell Raman spectroscopy in Saccharomyces cerevisiae, we demonstrate that replacing macro-heterogeneous promoters with homogeneous alternatives improves yield up to threefold in a metabolic pathway, highlighting promoter heterogeneity as an important consideration for strain design.

We show that transplanting an engineered leaf-mimetic microvascular network after experimental stroke promotes integration with host vessels and enhances neovascularization. The treatment improves cerebral perfusion, reduces infarct volume, and promotes neurological recovery while reshaping the immune–vascular microenvironment, providing a preclinical strategy for reconstructing peri-infarct microcirculation after ischemic stroke.

An engineered RNA-guided bridge recombinase system enables programmable, scarless chromosomal rearrangements in plant and mammalian cells. Co-optimization of the bridge RNA scaffold and bacterial recombinase ISCro4 improves activity by up to 29.8-fold, supports single-adeno-associated virus delivery, and enables a 315-kb inversion that rewires gene expression and confers herbicide resistance in rice.

Erythrocyte-based therapeutic delivery is valued for cargo protection and prolonged circulation, but this passive-carrier focus ignores the programmable intravascular interfaces now possible with erythrocytes. We propose a function-guided framework that matches designs to desired outcomes, serving as a guide to when erythrocytes could be the best choice for use as delivery vehicles.

Microbial co-culture provides a route to functional bacterial cellulose materials, but dynamic cultivation often compromises matrix formation. This study introduces a polydopamine-mediated platform that enables template-guided fabrication and modular protein functionalization of bacterial cellulose hydrogels.

Biotechnology companies must carefully consider the choice of the first disease indication for their new drug. There are several key elements that can help guide this critical decision. Drawing on years of experience, this article provides an ‘Indication Checklist’ with recommendations designed to help.

The label ‘engineered living materials’ groups devitalized mycelium composites with metabolically active biosensors, applying shared metrics to systems with fundamentally different failure modes, safety profiles, and engineering requirements. This forum proposes a four-class operational taxonomy, a Maximum Agency Potential classification principle, and a minimum reporting standard that classify systems by biological agency dependence during use.

Yeasts are promising cell factories, yet native glycolysis-driven overflow metabolism restricts NADPH-dependent biosynthesis. Uncovering the master flux regulator, CMR (central metabolism regulator), and building a pentose phosphate pathway-dominant chassis with heterologous phosphoketolase–phosphotransacetylase reinforcement enabled engineered Ogataea polymorpha to accumulate free fatty acids at 41.7 g/l, delivering a tunable platform for diverse NADPH-demanding bioproduction.

Recent FDA-approved gene-editing therapies illustrate not only the transformative potential of biotechnologies using CRISPR (clustered regularly interspaced short palindromic repeats)-derived ribonucleoproteins in treating a broad range of diseases but also the spectrum of possible molecular variations CRISPR therapeutics can adopt. These include exagamglogene autotemcel, an ex vivo therapy for hemoglobinopathies using CRISPR nuclease Cas9, and kayjayguran abengcemeran, an in vivo therapy using a protospacer adjacent motif-altered base-editing Cas9 variant for an ultra-rare metabolic disorder. Together, these therapies underscore how far CRISPR has advanced beyond its original use as a tool in biological/biomedical research. In this opinion article, we argue that as CRISPR biotechnologies advance beyond the relative simplicity of in vitro applications, our understanding must also evolve to address the challenges of optimizing ‘on-target’ and ‘off-target’ mutational activities across the diverse contexts in which they occur.

Achieving robust adhesion in wet and biological environments remains a major challenge in biotechnology and medicine. Coacervates are emerging as versatile adhesive platforms that function effectively under hydrated conditions. Their fluid-like nature enables efficient spreading at interfaces, while subsequent mechanical reinforcement stabilizes adhesion without permanent curing. In this review, we present a unifying framework in which adhesion arises from the interplay of interfacial wetting, multivalent interactions, viscoelastic energy dissipation, and kinetic arrest. We discuss how designing phase behavior and arrest dynamics can transform coacervates into functional bioadhesive interfaces for tissue sealing, drug delivery, and biointerface engineering. Finally, we outline challenges in predictive design, spatiotemporal control over arrest, and clinical translation, highlighting adhesive coacervates as multifunctional materials for complex wet environments.

Cryopreservation is essential to cell therapy manufacturing and efficacy. This work presents a biobanking strategy and formulation that significantly improve post-thaw cell expansion, functionality, and in vivo therapeutic efficacy compared to conventional cryopreservation approaches. Biobanking translatability was assessed using chimeric antigen receptor T cells that target hematological or solid tumors and multipotent stem cells.

Unconventional T cells (UTCs), including γδ T cells, mucosal-associated invariant T cells, and natural killer T cells, recognize conserved nonpeptide antigens through semi-invariant T cell receptors in an human leukocyte antigen-independent manner, making them attractive candidates for broadly applicable immunotherapies. However, their clinical translation remains limited by poor spatiotemporal control of activation, functional exhaustion, and insufficient tissue homing in vivo, particularly in solid tumors. Biomaterial-based delivery systems provide a promising strategy to overcome these barriers by enabling localized and sustained delivery of UTC ligands, cytokines, and nucleic acids within diseased tissues. Through precise in situ programming of UTC responses, these platforms may enhance therapeutic efficacy and safety. This review summarizes current biomaterial-based strategies and discusses emerging opportunities for in situ UTC programming in human cancers.

Encapsulation enables microbial technologies across agriculture, biotechnology, and biomedicine by protecting microorganisms from environmental and process-related stresses while extending their functional performance. Natural materials, including polysaccharides such as alginate and chitosan, and biomineral nanoparticles, are emerging as key enablers of encapsulation performance, while supporting sustainability, scalability, and industrial implementation. In this review, we analyze recent advances in natural polymer- and biomineral-based encapsulation systems, focusing on how material selection, encapsulation architecture, and microbial metabolism shape engineered microenvironments. We further discuss how encapsulation becomes technologically and environmentally relevant only when functional gains justify material and processing costs. Finally, we argue for a conceptual shift in encapsulation strategies: from protective supports toward bioinspired microhabitats and living microcapsules capable of programmable microbial functions.

Dairy proteins are among the most nutritionally and functionally valuable proteins used in food, clinical nutrition, and infant nutrition, yet their supply remains structurally linked to livestock production and dairy processing streams. Precision fermentation offers, based on proven technology, a route to produce individual milk proteins independently of animal agriculture while preserving their molecular identity and application potential. Recent advances in host engineering, secretion capacity, and bioprocess optimization have moved recombinant milk proteins from proof-of-concept toward industrial relevance. However, not all milk proteins are equally tractable fermentation targets. In this opinion article, we examine β-lactoglobulin, α-lactalbumin, and caseins through the lens of nutritional value, functionality, manufacturing complexity, and commercial readiness. We argue that future success will depend less on sequence expression alone than on scalable biomanufacturing technology and know-how, post-translational fidelity, and application-driven target prioritization.

Can Power-to-Gas become Power-to-Chemicals? By engineering methanogenic archaea for pilot-scale leucine production from H2 and CO2, we demonstrate that renewable gases can be transformed into valuable chemicals through bioprocess development and scale-up. A techno-economic analysis charts routes toward industrial implementation and a circular bioeconomy.

Biotechnology and biopharma rely on detailed genome annotations for cell-line engineering, yet most production hosts are nonmodel organisms with limited resources linking sequence to physiology across space and time. A complete four-dimensional genome annotation for Chinese hamster ovary (CHO) cells that links sequence, networks, spatial constraints, process state, and passaging history does not yet exist; current efforts instead provide partial layers that must be connected into an actionable framework. In this opinion article, we illustrate this framework for CHO cells, the dominant platform for recombinant protein biologics. Building such resources on a genomic foundation could reduce trial and error in biologics manufacturing by making cell line and bioprocess design more predictable, transparent, and reproducible.

We developed a Bacillus thuringiensis ΔcdsR chassis combined with AlphaFold3-guided protein discovery to enable safe and efficient production of insecticidal proteins. This platform links computational prediction with functional validation, offering a scalable strategy for developing next-generation, environmentally friendly biopesticides for sustainable pest management.

A scalable 4D biofabrication process combines high-cell-density bioprinting, alginate dissolution, and perfusion culture to generate scaffold-free bone-forming implants. The constructs undergo endochondral ossification in vivo, forming cortical and trabecular bone with bone marrow compartments, while scale-up enables the production of human-sized proof-of-concept implants.

Electric cues (ECs) permeate microbial habitats, yet electrosensing, the ability of microorganisms to detect and respond to these cues, remains largely overlooked. We distinguish four principal EC types [electric fields (EFs), electrode potentials, redox signals, and electromagnetic induction] and map each to its biological sensing mechanism. Recent findings reveal that cable bacteria respond to dynamic EFs through electromagnetic induction, a candidate sensing mechanism that is absent from existing models. We synthesize conserved sensing strategies primarily in bacteria, with emerging evidence in eukaryotes, and assess applications in bioenergy, bioremediation, and electroceutical therapy. Realizing this potential requires moving beyond static-field models toward experimental frameworks that capture the full temporal complexity of natural electric landscapes.

Preventing dietary exposure to toxic metals remains an unmet challenge. We engineered probiotics that sense and sequester arsenite in the gastrointestinal tract, reducing its systemic absorption and promoting its fecal elimination. This study establishes a programmable synthetic biology strategy for protecting against environmental toxicants.

Logic-gated chimeric antigen receptors (CARs) enable engineered immune cells to integrate multiple molecular and environmental inputs, improving therapeutic precision, safety, and resistance to antigen escape. As diverse logic-gated CAR architectures have emerged, differences in design principles and terminology have complicated comparisons across studies. This review presents a unified framework for classifying logic-gated CARs according to Boolean logic and biological signal integration, encompassing YES, OR, AND, INHIBIT (AND-NOT), sequential AND-YES/NOT, and hybrid architectures. We compare these systems based on computational logic, molecular mechanisms, reversibility, modularity, and clinical translatability and summarize the evolving clinical landscape of programmable immune cell therapies. This framework provides a practical reference for interpreting, designing, and translating next-generation logic-gated CAR systems.