Nature Nanotechnology, Published online: 29 April 2026; doi:10.1038/s41565-026-02164-7Modular RNA nanostar motifs spontaneously assemble into programmable synthetic condensates in the nucleus and cytoplasm, with RNA design controlling localization, sequence-specific target recruitment and orthogonal assembly.

Many bacterial defense systems restrict phage infection by breaking the molecule NAD+ to its constituents, adenosine diphosphate ribose (ADPR) and nicotinamide (Nam). To counter NAD+ depletion-mediated defense, phages evolved NAD+ reconstitution pathway 1 (NARP1), which uses ADPR and Nam to rebuild NAD+. Here we report a bacterial defense system called aRES, involving RES-domain proteins that degrade NAD+ into Nam and ADPR-1″-phosphate (ADPR-1P). This molecule cannot serve as a substrate for NARP1, so that NAD+ depletion by aRES defends against phages even if they encode NARP1. We further discover that some phages evolved an extended NARP1 pathway capable of overcoming aRES defense. In these phages, the NARP1 operon also includes a specialized phosphatase, which dephosphorylates ADPR-1P to form ADPR, a substrate from which NARP1 then reconstitutes NAD+. Other phages encode inhibitors that directly bind aRES proteins and physically block their active sites. Our study describes new layers in the NAD+-centric arms race between bacteria and phages and highlights the centrality of the NAD+ pool in cellular battles between viruses and their hosts. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, ERC-AdG GA 101018520 Israel Science Foundation, MAPATS grant 2720/22 Deutsche Forschungsgemeinschaft, SPP 2330, grant 464312965 Minerva Foundation with funding from the Federal German Ministry for Education and Research research grant from Magnus Konow in honor of his mother Olga Konow Rappaport Ministry of Aliyah and Immigrant Absorption, https://ror.org/05aycsg86 Clore Scholars Program

Structural and functional analyses elucidate the mechanisms by which two ATP-independent RNA chaperones, Ro60 and La, recognize and unfold misfolded RNAs. Diverse noncoding RNAs are associated with this chaperone machine, supporting a wide-ranging role in maintaining RNA homeostasis.

The cell-free biogenesis of the protein translation machinery is essential for the creation of a self-regenerating synthetic cell. Here the authors synthesise all 30 E. coli translation proteins in a ...

The first known outbreak of syphilis in Europe began at the turn of the 16th century, but on the distant continent of South America, the pathogen's history goes much deeper than that.

Malaria parasites move on helical trajectories when infecting their hosts. Now it is shown that they use right-handed chirality to control their motion patterns, and that this chirality is linked to t...

The reconstitution of complex biological processes in cell-free systems can support the detailed characterisation of biochemical mechanisms which are difficult to probe in vivo. Here authors present a...

Nature Nanotechnology, Published online: 10 December 2025; doi:10.1038/s41565-025-02058-0A microfluidic-free platform of miniaturized compartments displays on-chip-synthesized antigen gradients for quantitative epitope mapping of monoclonal antibodies and profiling of human sera and of human receptor–viral antigen interactions.

Self-assembly processes in biological and synthetic biomolecular systems are often governed by the spatial separation of biochemical processes. Whi...

Purification of active ribosomes is a prerequisite to studying ribosome functions. However, conventional purification methods such as ultracentrifugation, affinity tagging, and specialized chromatogra...

Cell-free protein synthesis (CFPS) is one approach to address the increasing demand for complex recombinant proteins in various applications, especially in the pharmaceutical sector. CFPS offers a var...

Nuclear biomolecular condensates are functional sub-compartments within the cell nucleus. Here, the authors develop a synthetic DNA protonucleus that enables RNA transcription and condensation into di...

Climate change made 213 historical heatwaves reported over 2000–2023 more likely and more intense, to which each of the 180 carbon majors (fossil fuel and cement producers) substantially contributed.

The programmability of synthetic cells, comprising lipid vesicles that are capable of imitating the structure and function of living cells, facilitates their application as drug delivery devices. Now,...

tRNAs are essential for translating genetic information into proteins. Here, the authors develop a method to synthesize all 21 essential tRNAs from a single DNA in vitro, enabling protein production a...

Synthetic cells encapsulating cell-free protein synthesis machinery are currently limited to laboratory use due to preservation challenges. They are typically produced and used immediately. We present...

Plasmids remain by far the most common medium for delivering engineered DNA to microorganisms. However, the reliance on natural plasmid replication mechanisms limits their tunability, compatibility, a...

The study of “resource allocator” bacteriophage T7 RNA polymerase (T7RNAP) has garnered significant interest, particularly for optimizing transcriptional systems in microbial cell factories (MCFs). Mo...

The One-Pot PURE (Protein synthesis Using Recombinant Elements) system simplifies the preparation of traditional PURE systems by coculturing and purifying 36 essential proteins for gene expression in ...

Cell-free systems are emerging as powerful platforms for synthetic biology with widespread applications in both fundamental research, such as artificial cell construction, and practical uses like recombinant protein production. Among these, cell-free protein synthesis (CFPS) plays a crucial role in gene expression for various downstream applications. However, the development of CFPS systems based on certain chassis, such as Bacillus subtilis, still remains limited due to their low in vitro productivity. Here, we report the development of a highly productive CFPS system derived from an engineered B. subtilis 164T7P strain, which contains a genomic integration of the T7 RNA polymerase gene. This modification allows the preparation of cell extracts that inherently contain T7 RNA polymerase, enabling T7 promoter-based transcription without the supplementation of purified T7 RNA polymerase in CFPS reactions. Through systematic optimization of cell extract preparation and key reaction parameters, we achieved the synthesis of 286 ± 16.7 μg/mL of sfGFP in batch reactions, with yields increasing to over 1100 μg/mL in a semicontinuous format that can replenish substrates and remove inhibitory byproducts. We further demonstrated the system’s versatility by using it for two synthetic biology applications: prototyping ribosome binding site (RBS) elements and synthesizing pulcherriminic acid─a bioactive cyclodipeptide. The system successfully characterized RBS performance, with in vitro and in vivo rankings correlating with predicted strengths, and expressed two active biosynthetic enzymes (cyclodipeptide synthase─YvmC and cytochrome P450 enzyme─CypX), leading to the production of pulcherriminic acid. Overall, our B. subtilis-based CFPS system offers a robust platform for high-yield protein synthesis, in vitro prototyping of gene regulatory elements, and natural product biosynthesis, highlighting its broad potential for synthetic biology and biotechnology applications.

An in vitro system is capable of sustainably regenerating 20 aminoacyl-tRNA synthetases toward artificial cells.

A biohybrid system is presented for mimicking infections in both cellular and tissue contexts. Droplet interface bilayers (DIBs) are spatio-temporally controlled to enable antibiotic addition, withdr...

This perspective offers a cross-disciplinary roadmap toward synthetic life that does not shy away from technical and non-technical challenges, ethical concerns, and provocative implications, embracing...

Cell-free gene expression (CFE) systems are often constrained by numerous biochemical components required to maintain biocatalytic efficiency. Here, the authors propose a droplet-AI combined approach ...

A split polymerase is used to develop a plug-and-play cell-free biosensor platform for point-of-care protein detection.

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Enzymes exist in ensembles of states that encode the energetics underlying their catalysis. Conformational ensembles built from 1231 structures of 17 serine proteases revealed atomic-level changes acr...