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...

Chromatin structure is regulated by chemical modifications of histone proteins, but measuring these at single-cell resolution has been challenging. Here, the authors develop a mass spectrometry-based ...

Here they show that PPARα-dependent mitochondrial programming promotes the differentiation of pluripotent stem cell-derived β cells. Targeting mitochondria has the potential to improve β cell replacem...

Neuronal function depends on mitochondria, but little is known about their organization across neurons. Using an electron microscopy Drosophila connectome, we uncovered quantitative rules governing th...

Neuronal function depends on mitochondria, but little is known about their organization across neurons. Using an electron microscopy Drosophila connectome, we uncovered quantitative rules governing th...

A forward genetic screen in Caenorhabditis elegans reveals that decreased levels of the ferredoxin FDX2 suppress the loss of frataxin in worms and in mice by relief of FDX2 inhibition of fra...

A forward genetic screen in Caenorhabditis elegans reveals that decreased levels of the ferredoxin FDX2 suppress the loss of frataxin in worms and in mice by relief of FDX2 inhibition of fra...

ABSTRACT. For post-docs pursuing an academic career, the transition to a group leader position can be a notoriously difficult one, not least because the availability of necessary support and training ...