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Optimized SORT LNPs enable precise and long-lasting base editing in dual organs in a disease mouse model.

Barcoding aids in the optimization of lipid nanoparticles. Here, the authors report on multiplexed mRNA barcoding that enables high-resolution spatiotemporal profiling of lipid nanoparticles, linking accumulation kinetics to functional delivery and revealing zonal liver targeting.

A screen of lung-targeting lipids revealed lipid nanoparticles offering improved delivery of mRNA and genome editors to lungs. Probing structure–activity relationships revealed a unique ‘tripod-like’ shape associated with the improvements.

Here, the authors profile bacterial engraftment in UC patients receiving FMT from a single donor and placebo samples to estimate noise, showing a significant level of false-positive engraftment, which confounds the prediction of true engraftment, while analyzing engraftment across multiple patients from a single donor enhances the accuracy of detection.

The addition of selective organ targeting molecules to nanoparticles allows the specific targeting of extrahepatic tissues, enabling gene editing of distinct cell populations outside the liver.

Roughly 10% of Cystic Fibrosis (CF) patients still have no effective medicine to take. Lung Selective Organ Targeting (SORT) Lipid Nanoparticles can efficiently deliver Cas9 mRNA, sgRNA, and donor ssDNA templates for precise homology-directed repair-mediated gene correction in ex vivo and in vivo CF models.

Ongoing chikungunya virus replication leads to the accumulation of inflammatory macrophages and CD4⁺ T cells in joint-associated tissues. Inhibition of chikungunya virus replication during chronic disease reduced viral RNA and joint inflammation in mice.

Imprinting by influenza viruses can cause a deleterious shift of nearly the entire memory recall response against key, conserved epitopes.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

A sample of US producers’ worldviews on sustainable meat production fall into three categories, which can guide decision-makers towards actions with broad support and highlight those requiring more targeted efforts.

Here, Deol et al. use genetic screens in gene-edited reporter cell lines to identify regulators of ferroptosis suppressor protein 1 (FSP1) expression and stability. They show that vitamin B2 metabolism stabilizes FSP1 through flavin adenine dinucleotide binding, preventing its degradation and ferroptosis sensitization.

Frank et al. introduce Euclidean fast attention, a linear-scaling framework for 3D data. By leveraging Euclidean rotary encodings, the method overcomes the quadratic cost of standard attention to accurately capture long-range effects in physical systems.

The evolutionary origin of tumours remains largely unknown. Here, Domazet-Lošo et al. show evidence for naturally occurring tumours in the freshwater polyp, Hydra, and suggest that tumours have deep evolutionary roots.

Klose and colleagues show that the neuropeptide vasoactive intestinal peptide (VIP) acts on LGR5⁺ epithelial stem cells in the gut to restrain their proliferation and differentiation to secretory cell types. This VIP–VIPR1 interaction acts to limit type 2 immune responses.

Peter J. Smith, who once accepted a NATO Fellowship because it was the only support available for work in a nonuniversity research institution in the United States, discusses NATO's involvement in civil science.

Connectome-seq allows access to connectomic and transcriptomic information in high throughput, using an RNA barcoding strategy and isolation of synaptosomes, followed by single-nucleus and single-synaptosome RNA sequencing.

Early-life exposure to allergens triggers a distinct local mode of dendritic cell activation in neonatal skin without requiring migration to lymph nodes, which shapes responses to allergens in later life.

This study applies machine learning to fMRI data to map developmental variations in functional connectivity, uncovering heterogeneity across individuals and cortical regions that predicts neurocognitive maturation in youth.

A tunable granular biomaterial matrix is developed to support long-term bioprinting. Stress relaxation at high strains and long timescales is shown to be important for tissue self-organization in intestinal organoids.

 Artificial intelligence goes beyond the current state of the art by discovering unknown, faster sorting algorithms as a single-player game using a deep reinforcement learning agent. These algorithms are now used in the standard C++ sort library.

CRISPR–Cas9 screening identifies CLCC1 as a factor that increases neutral lipid flux to prevent hepatic steatosis and promotes nuclear pore complex assembly by promoting membrane bending and fusion.

An improved faba bean reference genome and resequencing of winter and spring faba bean accessions identify genetic determinants of winter hardiness.

A combination of ancestral reconstruction and deep mutational scanning to examine the genotype–phenotype maps of steroid receptors shows that the properties of ancestral genotype–phenotype maps determine the lineage-specific evolution of DNA specificity.

This protocol details the preparation of selective organ-targeting lipid nanoparticles by several methods, their physical characterization, and in vitro/in vivo mRNA delivery evaluation.

An ion pump that does not require redox reactions to drive aqueous ions against forces is demonstrated, and may find applications in selective ion separation and water desalination.

Several models have been proposed to explain chromosome segregation during anaphase. By using chemical optogenetics, a study now identifies antiparallel sliding of central spindle microtubules as the driving force of chromosome segregation, while depolymerization of kinetochore microtubules primarily limits spindle elongation.

Insights into the mechanism by which phosphatidylserine functions as a non-classical inhibitory molecule during T cell exhaustion, and how phosphatidylserine-targeting antibodies enhance T cell responses are explored.

DIAMOND DeepClust provides an ultra-fast clustering method for organizing the protein universe of life at low sequence identity, enabling large-scale dimensionality reduction and improving downstream structure prediction with AlphaFold2.

A class of cationic—amidine-based degradable—lipids can now be readily synthesized through a tandem multi-component amine–thiol–acrylate conjugation reaction. Mechanistic studies provided key insights, from which the observed lead lipid enabled mRNA delivery to multiple organs, highlighting the potential for developing mRNA vaccines and therapeutics to treat various diseases.

Myelopoiesis in response to a parasitic worm infection and the mechanism selective to this form of parasite are revealed.

Many viral vaccine antigen candidates are transmembrane glycoproteins, and their development requires methods which allow their biophysical characterization. Here authors present an optimized nanodisc assembly platform which provides reproducible, scalable, and accurate replication of the vaccine candidates for detailed analysis.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Nitazenes are potent synthetic opioids that are difficult to detect. Here, authors computationally redesign a plant receptor to create sensitive sensors capable of detecting diverse nitazenes and their metabolites in biological samples.

A peptide display method was developed, revealing that a kinase important for infection by Salmonella and related pathogens detects specific human antimicrobial peptides, possibly reflecting bacterial adaptation to distinct host locations.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

Computationally designed genetically encoded proteins can be used to target surface proteins, thereby triggering endocytosis and subsequent intracellular degradation, activating signalling or increasing cellular uptake in specific tissues.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

Izar and colleagues review the insights into cancer biology gained via single-cell analyses and spatial profiling and overview the challenges and opportunities associated with the implementation of these approaches to guide clinical discovery.

By incorporating unnatural amino acids into proteins, Elliott et al. label, image and identify proteins in specific cells in a developing fly under physiological conditions.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.