For proper mitochondrial inheritance, paternal sperm mitochondria must be eliminated. Here, authors identify ALKB-1 mediated tRNA demethylation as essential for this clearance in Caenorhabditis elegan...

For proper mitochondrial inheritance, paternal sperm mitochondria must be eliminated. Here, authors identify ALKB-1 mediated tRNA demethylation as essential for this clearance in Caenorhabditis elegan...

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Co-cultivation of the cellulose-producing bacterium with the microalga enables bulk formation of bacterial cellulose under static incubation, with photosynthetically active oxygen-generating sites th...

Dynamic extracellular matrix mechanics regulate fundamental cellular processes, yet precise control over spatiotemporal rigidity modulation remains challenging. Protein-based photoresponsive hydrogels...

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Hexokinase detachment from the outer mitochondrial membrane is shown to support aerobic glycolysis in cancer cells. Differential localization of the HK1 isoform to the outer mitochondrial membrane, co...

Environmental adaptation often involves a shift in energy utilization toward mitochondrial fatty acid oxidation, which requires carnitine. Besides dietary sources of animal origin, carnitine biosynthe...

Lucid Scientific is the maker of Resipher - the world's first handheld cell culture monitor to measure real-time oxygen consumption from inside an incubator.

Zhang et al. characterize the mitochondrial inner membrane subdomain organizer (MISO) protein, which responds to inner mitochondrial membrane stress by inducing membrane subdomains promoting homeostat...

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.

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