Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Rathmell and colleagues show that metabolic reprograming of regulatory T cells is associated with severity of critical illness in patients with and without sepsis.

Mitochondria that are transported from satellite glial cells in dorsal root ganglia to peripheral sensory neurons through tunneling nanotube-like structures provide protection against peripheral neuro...

Mitochondria that are transported from satellite glial cells in dorsal root ganglia to peripheral sensory neurons through tunneling nanotube-like structures provide protection against peripheral neuro...

How the complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth is explored.

Sepsis-associated encephalopathy (SAE) is a common and serious complication of sepsis that leads to acute brain dysfunction and long-term cognitive impairment. We used widely targeted LC–MS/MS plasma ...

STING–type-I interferon pathway regulates the immunogenicity of several cancer types, including head and neck squamous cell carcinoma. Here the authors describe that glutamine metabolism in the tumour...

Colina-Tenorio et al. show that MICOS interacts with the Cox1 and Cox3 assembly modules and facilitates respiratory complex IV biogenesis. By recruiting assembly factors and the mitochondrial multifun...

Xiao et al. reveal that sorting nexin 17 (SNX17) promotes the synthesis of uridine phosphorylase 1 (UPP1) in tumor cells, leading to a decrease in uridine concentration within the tumor microenvironme...

Recombinant adeno-associated viral (rAAV) vectors are a leading platform for in vivo gene therapy, valued for their excellent safety, broad serotype diversity, and scalable production. Targeted delivery through capsid display of ligands holds great promise, yet current retargeting strategies often rely on extensive capsid re-engineering and restrict the use of ligands incompatible with intracellular expression systems. Here, we present a modular AAV retargeting platform that, for the first time, employs the SpyTag/SpyCatcher system via genetic integration into the AAV2 capsid. SpyTag is a small peptide that forms a covalent, irreversible bond with its protein partner, SpyCatcher, allowing site-specific ligand coupling under physiological conditions. Inserting SpyTag into surface-exposed capsid sites enabled postassembly functionalization of AAVs with SpyCatcher-fused targeting proteins. As proof of concept, we used SpyCatcher fusions with designed ankyrin repeat proteins (DARPins) specific for EGFR, EpCAM, and HER2. This conferred highly specific transduction of corresponding cancer cell lines with minimal off-target activity. Therapeutic potential was demonstrated by delivering a suicide gene, inducing selective cancer cell killing upon prodrug administration. This “one-fits-all” platform allows rapid and flexible retargeting without significantly altering the underlying vectors genome or production process. It supports the incorporation of large or complex ligands not amenable to genetic fusion and facilitates high-throughput preclinical evaluation strategies. By uniting capsid engineering with modular ligand display, our approach provides a scalable and versatile framework for precision gene delivery, broadening the applicability of rAAV in both therapeutic and discovery settings.

Through metabolic remodeling, tumor cells can modulate neighboring CD8+ T cell function via metabolites. A recent study by Ma et al., published in Immunity, reveals that tumor-cell-derived succinate exhibit an antitumor immune effect, promoting the survival and stemness of CD8+ T cells by enhancing mitochondrial fitness and inducing epigenetic reprogramming.

Oxidative stress is a major driver of cardiovascular disease; however, the fast changes in cellular metabolism caused by short-lived reactive oxygen species (ROS) remain ill-defined. Here, we characte...

Here the authors show that mitochondrial RNA leaks into the cytosol of senescent cells through sublethal apoptosis, driving inflammation. Blocking this pathway improves outcomes in Metabolic Dysfuncti...

Nature Cell Biology - The authors optimize an in vitro human epiblast model, which they utilize to show that early TGFβ family inhibition prevents epithelial identity, whereas it is...