Viral protease-initiated lytic cell death as a universal antiviral mRNA therapy.

July 20, 2026| Source: Cell

While gasdermin (GSDM)-mediated pyroptosis is a potent immune effector, its antiviral potential remains largely untapped. Here, we introduce viral protease-initiated lytic cell death (VID), a universal mRNA therapeutic platform inspired by the modular architecture of GSDM and the clinical success of mRNA vaccines. By engineering gasdermin-D (GSDMD) to harbor viral protease-specific cleavage motifs, we generated VID activators (VIDAs) that selectively trigger lytic cell death in virus-infected cells. Using hepatitis A virus (HAV) as a model, lipid nanoparticle (LNP)-encapsulated VIDA mRNA abolished viral replication and shedding in vivo and mitigated liver injury through a coordinated "kill-and-alert" mechanism that primes bystander immunity. The platform's versatility was further demonstrated against Zika virus (ZIKV) and SARS-CoV-2. Leveraging a generative artificial intelligence (AI) framework, we designed de novo cleavage motifs for the SARS-CoV-2 main protease, yielding optimized VIDAs with superior antiviral potency. Collectively, our study establishes VIDA mRNA as a versatile, broadly applicable strategy for combating diverse viral threats.

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Integrating cooperative breeding with reciprocity and culture extends Hamilton's rule to humans.

We study how kinship and reciprocity shape giving and child care support in societies with limited access to markets. Extending Hamilton's rule to incorporate reciprocity, we test it using behavioral data from dictator games and surveys in remote matrilocal and patrilocal villages of northeast India (N = 406 parents of young children). We replicate with data from urban Manila neighborhoods (N = 301) and the Solomon Islands (N = 624). Consistent with predictions, transfers to recipients increase

Artificial IntelligenceOctober 15, 2026

Multi-omics atlas of chronic exercise.

Exercise reduces all-cause mortality, yet its molecular effects across organs, sexes, and circadian phases remain incompletely understood. We subjected mice to 8 weeks of voluntary wheel running and collected 22 tissues and plasma during active and inactive phases for bulk RNA sequencing, metabolomics, proteomics, and single-nucleus RNA and methylation sequencing. Exercise induced canonical fiber-type switching and widespread, tissue-specific remodeling, with the largest transcriptomic changes i

Artificial IntelligenceOctober 14, 2026

A microexon regulatory code reveals autism-linked genetic variation.

Neuronal microexons are a highly conserved class of alternative splicing events enriched in genes with critical functions in nervous system biology 1,2 . Microexon splicing is often disrupted in the brains of autistic individuals, and mice with microexon deficiencies display autism-like phenotypes 1,3,4 . However, the full landscape of microexons is not known, and the impact of genetic variation on these exons has not been systematically investigated. Here, through extensive transcriptome profil

Artificial IntelligenceOctober 13, 2026

Deep learning of fossil pollen morphology reveals 25,000 y of ecological change in eastern African grasslands.

Grass (Poaceae) pollen is largely overlooked in investigations of grassland evolution because the pollen of most species cannot be differentiated using traditional optical microscopy. However, the combination of superresolution microscopy and deep learning enables the capture and quantification of distinct morphological variation across the pollen of grass species. Using a semisupervised deep-learning strategy, we trained convolutional neural networks (CNNs) on superresolution images of known mo

Artificial IntelligenceOctober 13, 2026

Tyrosine phosphorylation unfolds nucleophosmin and disrupts its integration into the nucleolus.

Nucleophosmin (NPM1) is a multifunctional nucleolar protein essential for ribosome biogenesis, genome stability, and stress responses. Its integration into the nucleolus depends on its oligomerization and multivalent interactions that enable liquid-liquid phase separation (LLPS). Here, we investigate how tyrosine phosphorylation at Tyr17, Tyr29, and Tyr67 located within the interface between monomers at the N-terminal oligomerization domain regulates NPM1 structure and function. Replacing tyrosi