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SARS-CoV-2 Omicron XEC variant, a recombinant of JN.1 progeny, shows increased viral fitness and pathogenicity. Here, the authors show that the nucleocapsid mutation R204P enhances inflammation and suggest a growing role of non-spike mutations in viral evolution.

The fetal globin gene repressors BCL11A and ZBTB7A directly bind γ-globin gene promoter regions. Repressor binding is disrupted by naturally occurring point mutations located upstream of the transcriptional start site that are associated with hereditary persistence of fetal hemoglobin.

A detailed spatiotemporal roadmap of the human female and male reproductive tracts during key periods of sexual differentiation provides new cellular and molecular insights into how early axial gradients lead to specific cell lineages and tissue structures.

This study reports that wild boars are a node animal in a virus circulation network connecting different animal taxa. Wild boar viruses not only pose threats to the pig industry but also challenge wildlife conservation and public health.

TadA deaminases widely used in many base editors lack post-translational control in cells. Here the authors report a split adenine base editor (sABE) using chemically induced dimerisation (CID) to control the catalytic activity of TadA8e and show this can be used for PCSK9 gene editing in the mouse liver.

CRISPR-Cas9 mediated gene editing has begun to revolutionize molecular biology, but editing efficiencies can vary greatly between reagents. The authors show that the addition of single-stranded non-homologous DNA stimulates gene disruption by favouring error-prone DNA repair.

Reported is a recombineering pipeline for efficient and large-scale gene modification in the mouse malarial parasite Plasmodium berghei.

Hybrid gRNAs significantly increase targeted editing in the liver while simultaneously reducing unwanted bystander editing in humanized mouse models.

Activin receptor-like kinase 4 (ALK4) is frequently downregulated or mutated in cancers. Here the authors find that ALK4 loss promotes canonical TGF-β signaling and cancer progression through increasing TGF-β receptor N-linked glycosylation and subsequently stabilizing these receptors at the cell surface.

Manju Kurian and colleagues report heterozygous variants in KMT2B in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance. Their findings highlight a clinically recognizable form of dystonia and demonstrate a crucial role for KMT2B in the physiological control of voluntary movement.

Primary angle-closure glaucoma is a leading cause of blindness. Here, the authors identify rare deleterious variants in UBOX5 as risk factors and implicate BIP ubiquitination as a potential disease mechanism.

DNA damage can arise from natural cellular processes, but how cells prevent resulting mutations is unclear. Here, the authors show that the enzyme Polκ protects mouse tissues from mutations caused by endogenous guanine lesions, revealing how DNA repair and damage tolerance pathways cooperate to maintain genome integrity.

Targeted in situ sequencing directly maps editing rates at single-cell resolution in postmortem tissues to visualize base and prime editor delivery.

While prime editing is a promising technique, some genomic sites remain difficult to edit. Here the authors present fluoPEER, fluorescent prime editing and enrichment reporter, to rank the efficiency of pegRNAs and prime editor variants.

By mapping oxidatively damaged bases and abasic sites at single-nucleotide resolution in human cells, Takhaveev et al. observed transcription-related strand biases, patterns mirroring cancer mutational signatures, and captured the action of the anticancer drug irofulven.

The authors show that resistance to the antifungal 5-fluorocytosine in Cryptococcus deuterogattii is acquired more frequently in isolates with elevated mutation rate, and is associated with alterations in capsule biosynthesis and nucleotide metabolism.

RNA-guided CRISPR-associated transposases (CAST) are natural systems with broad potential in biotechnology. Here, the authors report compact type V-K CAST discovered from genome-resolved metagenomics and demonstrate targeted integration of a large transgene to a safe-harbor site in the human genome.

This study reports that Saffold virus, associated with respiratory, gastrointestinal, and neurological illnesses, uses both sulfated glycosaminoglycans and integrin αVβ8 as cooperative attachment receptors essential for viral entry.

Sézary syndrome is a T cell malignancy that has been poorly characterized at the genome level. In this study, Kielet al. perform whole-genome analyses and identify mutations in the JAK–STAT pathway and show that primary cells are sensitive to JAK inhibitors.

Analysis of the longest-lived mammal, the bowhead whale, reveals an improved ability to repair DNA breaks, mediated by high levels of cold-inducible RNA-binding protein.   

Whole-genome sequencing of 962 clear cell renal cell carcinomas from 11 countries shows geographic variations in somatic mutation profiles, including a mutational signature of unknown cause in 70% of cases from Japan.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

Pseudomonas aeruginosa H1-T6SS delivers effectors in response to exogenous T6SS attacks. In this study, a CRISPRi screen identifies pathways involved in P. aeruginosa resistance to T6SS effectors of Acinetobacter baylyi and Vibrio cholerae.

DNA double-stranded breaks threaten genome stability. Here, the authors show that transcript RNA serves as a repair template in human cells and identify Polζ as a key factor in RNA-templated DSB repair. This process can lead to intron deletion, resulting in a mutational signature in cancer genomes.

This study employs a functional genomic approach to identify a synthetic lethal interaction between CDS1 and CDS2 in uveal melanoma and other cancers, which may represent a potential therapeutic target.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Authors show that all individuals have asymmetrically glycosylated IgGs—the glycans on each of the Fc protomers are not identical. Asymmetrically monofucosylated IgGs drive dengue disease and are functionally similar to afucosylated IgGs.

The microbiota may mediate the differential responses to oral cholera vaccine (OCV). Here, the authors reveal that the presence of sphingolipid-producing bacteria is associated with the development of protective immune responses after OCV.

Fluidic force microscopy combines atomic force microscopy with microfluidic probes to enable measurement and manipulation of materials at sub-micrometre resolution. In this Primer, Zambelli et al. discuss the principles of fluidic force microscopy and applications in biological research and nanotechnology.

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

Current single-cell RNA sequencing methods struggle to comprehensively profile transcriptomes, with many lowly expressed transcripts remaining undetected. Here authors present a workflow for enhancing the detection of both transcripts and regions of interest in combination with a standard transcriptome profile.

In this attempt at xenotransplantation of a lung from a genetically modified pig into a brain-dead recipient, although the grafted lung initially maintained viability and functionality, antibody-mediated rejection rapidly occurred, contributing to xenograft damage.

Analysis of 14,106 tumor genomes highlights recurrent mutations in mitochondrial ribosomal RNA encoded within the mitochondrial genome. Mutations occur at hotspot positions and are under strong purifying selection in the germline.

Africa-specific genetic variation on chromosome 1 near CHD1L is associated with HIV replication in vivo.

Genomic integration of DNA templates is made more precise through microhomology-focused design.

Peptide-enabled ribonucleoprotein delivery for CRISPR engineering (PERC) uses an amphiphilic peptide reagent to mediate intracellular delivery of CRISPR enzymes for high-efficiency editing of stimulated immune cells and cultured hematopoietic stem and progenitor cells (HSPCs).

The antiviral protein SP140 negatively regulates Ifnb1 mRNA stability by directly repressing the expression of the immune regulator RESIST.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

DEAD-box helicase 6 (DDX6), the regulator of P-body assembly, is essential for the survival of acute myeloid leukemia (AML) cells. Here the authors report that DDX6 undergoes phase separation to preserve mRNA subsets in P-bodies, promoting branched-chain amino acid metabolism and chemoresistance in AML.

Defective ribonucleotide excision repair causes ID4, an indel cancer signature characterized by deletions of 2–5 base pairs.

Whole-genome sequencing and mutational signature analysis of 265 head and neck cancer samples collected from eight different countries provide insight into the vital contribution of tobacco smoke in disease etiology.

Here the authors identify TNIP1 as a risk factor for a fatal neurodegenerative disorder and discover specific genetic loci associated with the three main subtypes of this disorder. The findings highlight distinct disease mechanisms, emphasizing the roles of immunity and the notch signaling pathway.

While the emergence of immune checkpoint inhibitors has improved outcomes in patients with small cell lung cancer (SCLC), tumour that develop means of immune evasion become resistant. Here, the authors report that ERBB2 signalling induces loss of MHC Class I expression and subsequently immune evasion in preclinical models of SCLC.