Plasmids that replicate independently from chromosomes are valuable genetic tools for biological research. Dynamic control of plasmid copy number facilitates flexible regulation of the gene of interest or the genetic circuit installed in the plasmid. This useful strategy is being integrated into synthetic biology for metabolic reprogramming and biosensing applications.

DNA is an intelligent data storage medium due to its stability and high density. It has been used by nature for over 3.5 billion years. Compared with traditional methods, DNA offers better compression and physical density. DNA can retain information for thousands of years. However, challenges exist in scalability, standardization, metadata gathering, biocybersecurity, and specialized tools. Addressing these challenges is crucial for widespread implementation. Collaboration among experts, as well as keeping the future in mind, is needed to unlock the full potential of DNA data storage, which promises low energy costs, high-density storage, and long-term stability.

The IS200/605 transposons in prokaryotes are known to harbor programmable endonucleases. Despite carrying their own transposable elements, no such effector has been characterized in eukaryotes. Saito et al. recently reported compact and programmable RNA-guided eukaryotic endonucleases, called Fanzors, that can induce targeted genetic modifications, thus expanding the genome-editing toolbox.

Advancements in materials-driven mechanobiology have yielded significant progress. Mechanobiology explores how cellular and tissue mechanics impact development, physiology, and disease, where extracellular matrix (ECM) dynamically interacts with cells. Biomaterial-based platforms emulate synthetic ECMs, offering precise control over cellular behaviors by adjusting mechanical properties. Recent technological advances enable in vitro models replicating active mechanical stimuli in vivo. These models manipulate cellular mechanics even at a subcellular level. In this review we discuss recent material-based mechanomodulatory studies in mechanobiology. We highlight the endeavors to mimic the dynamic properties of native ECM during pathophysiological processes like cellular homeostasis, lineage specification, development, aging, and disease progression. These insights may inform the design of accurate in vitro mechanomodulatory platforms that replicate ECM mechanics.

In human vascular anatomy, blood flows from the heart to organs and tissues through a hierarchical vascular tree, comprising large arteries that branch into arterioles and further into capillaries, where gas and nutrient exchange occur. Engineering a complete, integrated vascular hierarchy with vessels large enough to suture, strong enough to withstand hemodynamic forces, and a branching structure to permit immediate perfusion of a fluidic circuit across scales would be transformative for regenerative medicine (RM), enabling the translation of engineered tissues of clinically relevant size, and perhaps whole organs. How close are we to solving this biological plumbing problem? In this review, we highlight advances in engineered vasculature at individual scales and focus on recent strategies to integrate across scales.

CRISPR/Cas9 gene technology is transported as RNA from transgenic roots to distal parts of unmodified grafted scion, where it is translated into proteins to induce heritable mutagenesis at desired loci. This technique has the potential to produce transgene-free and genetically stable plants in difficult-to-propagate and near-extinct species.

Current in vitro intervertebral disc (IVD) models do not fully recapitulate the complex mechanobiology of native tissue, and so far there is no strategy to effectively evaluate IVD regeneration. The development of a modular microfluidic on-chip model is expected to enhance the physiological relevance of experimental data leading to successful clinical outcomes.

Exosome-based strategies constitute a promising tool for therapeutics, avoiding potential immunogenic and tumorigenic side-effects of cell therapies. However, the collection of a suitable exosome pool, and the need for high doses with conventional administration approaches, hamper their clinical translation. To overcome these challenges, versatile exosome collection strategies together with advanced delivery platforms may represent major progress in this field. Microfluidics enables large-scale gathering of both natural and synthetic exosomes for their implementation into bioinks, while 3D-bioprinting holds great promise in regenerative medicine with the use of exosome-loaded scaffolds that mimic the target tissue with controlled pharmacokinetics and pharmacodynamics. Hence, the combination of both strategies might become the key for the translation of exosome therapies to clinical practice.

Aptamers are single-stranded oligonucleotides that bind to their targets via specific structural interactions. To improve the properties and performance of aptamers, modified nucleotides are incorporated during or after a selection process such as systematic evolution of ligands by exponential enrichment (SELEX). We summarize the latest modified nucleotides and strategies used in modified (mod)-SELEX and post-SELEX to develop modified aptamers, highlight the methods used to characterize aptamer-target interactions, and present recent progress in modified aptamers that recognize different targets. We discuss the challenges and perspectives in further advancing the methodologies and toolsets to accelerate the discovery of modified aptamers, improve the throughput of aptamer-target characterization, and expand the functional diversity and complexity of modified aptamers.

Media representations of emerging biotechnologies in the media can influence public attitudes and have the potential to impact on policy decisions and law-making. We discuss the unbalanced portrayal of synthetic biology in Chinese news media and how it might affect the perceptions of the public, the scientific community, and decision-makers.

Proteogenomics (PG) integrates the proteome with the genome and transcriptome to refine gene models and annotation. Coupled with single-cell (SC) assays, PG effectively distinguishes heterogeneity among cell groups. Affiliating spatial information to PG reveals the high-resolution circuitry within SC atlases. Additionally, PG can investigate dynamic changes in protein-coding genes in plants across growth and development as well as stress and external stimulation, significantly contributing to the functional genome. Here we summarize existing PG research in plants and introduce the technical features of various methods. Combining PG with other omics, such as metabolomics and peptidomics, can offer even deeper insights into gene functions. We argue that the application of PG will represent an important font of foundational knowledge for plants.

Blue Biotechnology is developing rapidly worldwide. However, the Nagoya Protocol (NP), Responsible Research and Innovation (RRI) and other regulatory requirements in this field are falling behind. This article identifies the main RRI, NP, and regulatory gaps and provides key recommendations to mitigate these challenges.

If biomanufacturing can become a sustainable route for producing chemicals, it will provide a critical step in reducing greenhouse gas emissions to fight climate change. However, efforts to industrialize microbial synthesis of chemicals have met with varied success, due, in part, to challenges in translating laboratory successes to industrial scale. With a particular focus on Escherichia coli, this review examines the lessons learned when studying microbial physiology and metabolism under conditions that simulate large-scale bioreactors and methods to minimize cellular waste through reduction of maintenance energy, optimizing the stress response and minimizing culture heterogeneity. With general strategies to overcome these challenges, biomanufacturing process scale-up could be de-risked and the time and cost of bringing promising syntheses to market could be reduced.

Microbial consortia can complete otherwise arduous tasks through the cooperation of multiple microbial species. This concept has been applied to produce commodity chemicals, natural products, and biofuels. However, metabolite incompatibility and growth competition can make the microbial composition unstable, and fluctuating microbial populations reduce the efficiency of chemical production. Thus, controlling the populations and regulating the complex interactions between different strains are challenges in constructing stable microbial consortia. This Review discusses advances in synthetic biology and metabolic engineering to control social interactions within microbial cocultures, including substrate separation, byproduct elimination, crossfeeding, and quorum-sensing circuit design. Additionally, this Review addresses interdisciplinary strategies to improve the stability of microbial consortia and provides design principles for microbial consortia to enhance chemical production.

mRNA vaccines have won the race for early COVID-19 vaccine approval, yet improvements are necessary to retain this leading role in combating infectious diseases. A next generation of self-amplifying mRNAs, also known as replicons, form an ideal vaccine platform. Replicons induce potent humoral and cellular responses with few adverse effects upon a minimal, single-dose immunization. Delivery of replicons is achieved with virus-like replicon particles (VRPs), or in nonviral vehicles such as liposomes or lipid nanoparticles. Here, we discuss innovative advances, including multivalent, mucosal, and therapeutic replicon vaccines, and highlight novelties in replicon design. As soon as essential safety evaluations have been resolved, this promising vaccine concept can transform into a widely applied clinical platform technology taking center stage in pandemic preparedness.

Bacteria have evolved a diverse set of enzymes that enable them to subvert host defense mechanisms as well as to form part of the prokaryotic immune system. Due to their unique and varied biochemical activities, these bacterial enzymes have emerged as key tools for understanding and investigating biological systems. In this review, we summarize and discuss some of the most prominent bacterial enzymes used for the site-specific modification of proteins, in vivo protein labeling, proximity labeling, interactome mapping, signaling pathway manipulation, and therapeutic discovery. Finally, we provide a perspective on the complementary advantages and limitations of using bacterial enzymes compared with chemical probes for exploring biological systems.

The construction of synthetic microbial consortia has been considered a new frontier. However, maintaining artificial microbial communities remains challenging because the dominant strain eventually outcompetes the others. Inspired by natural ecosystems, one promising approach to assemble stable consortia is to construct spatial niches partitioning subpopulations and overlapping abiotic requirements.

Reconstructing the meniscus is not currently possible due to its intricate and heterogeneous structure. In this forum, we first discuss the shortcomings of current clinical strategies in meniscus repair. Then, we describe a new promising cell-based, ink-free 3D biofabrication technology to produce tailor-made large-scale functional menisci.

Iron-oxide-based biomagnetic nanocomposites, recognized for their significant properties, have been utilized in MRI and cancer treatment for several decades. The expansion of clinical applications is limited by the occurrence of adverse effects. These limitations are largely attributed to suboptimal material design, resulting in agglomeration, reduced magnetic relaxivity, and inadequate functionality. To address these challenges, various synthesis methods and modification strategies have been used to tailor the size, shape, and properties of iron oxide nanoparticle (FeONP)-based nanocomposites. The resulting modified nanocomposites exhibit significant potential for application in diagnostic, therapeutic, and theranostic contexts, including MRI, drug delivery, and anticancer and antimicrobial activity. Yet, their biosafety profile must be rigorously evaluated. Such efforts will facilitate the broader clinical translation of FeONP-based nanocomposites in biomedical applications.

CRISPR biosensors enable rapid and accurate detection of nucleic acids without resorting to target amplification. Specifically, these systems facilitate the simultaneous detection of multiple nucleic acid targets with single-base specificity. This is an invaluable asset that can ultimately facilitate accurate diagnoses of biologically complex diseases.