Angew. Chem.∣A Novel Targeted Delivery Strategy for the CRISPR/Cas9 System
This study has developed a novel strategy based on bioorthogonal reactions to achieve targeted enrichment of the CRISPR/Cas9 system at tumor sites, thereby enabling dual-targeted cancer immunotherapy. The researchers found that a tumor microenvironment–degradable hollow manganese dioxide (H-MnO2) nanoplatform can simultaneously enable selective in vivo labeling of tumor sites and activation of the cGAS-STING signaling pathway. Subsequently, lipid nanoparticles loaded with the CRISPR/Cas9 system accumulate in tumor tissues via bioorthogonal reactions and, by knocking down the protein tyrosine phosphatase N2 gene, further enhance the sensitivity of tumors to immunotherapy. In summary, this study provides a modular platform for precise in vivo gene editing and, by reshaping the tumor immune microenvironment, elicits robust antitumor responses, thereby offering strong support for the translational application of CRISPR technology in cancer immunotherapy.
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Advanced Science∣Mitochondrial Protein IFI27 Promotes the Thermogenic Mechanism in Adipocytes
This study first used transmission electron microscopy to demonstrate that the IFI27 protein is predominantly localized in the mitochondrial matrix. Subsequently, by generating gene-knockout mouse models and conducting a series of validation experiments, the researchers identified IFI27 as a novel regulator of mitochondrial metabolism and adaptive thermogenesis. On one hand, IFI27 specifically modulates the stability of SDHB in the mitochondrial matrix, thereby maintaining the normal function of succinate dehydrogenase; on the other hand, it interacts with the mitochondrial matrix protein HADHA, preserving its enzymatic activity and ensuring the proper functioning of the tricarboxylic acid cycle and fatty acid oxidation in brown adipose tissue (BAT)—the primary thermogenic organ—thus sustaining adaptive thermogenesis. In summary, this study elucidates the functional role of IFI27 in BAT and reveals its critical mechanisms in regulating mitochondrial metabolism and adapting to environmental changes.
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