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http://dx.doi.org/10.1186/s13148-024-01636-8 | DOI Listing |
: Sepsis (life-threatening organ dysfunction caused by a dysregulated host response to infection) causes millions of deaths worldwide annually. Sepsis-induced changes in brain regulatory functions remain understudied. Previous work demonstrated that cecal ligation and puncture (CLP, a murine model of sepsis) affected physiologic variables and serum cytokines and hormone levels.
View Article and Find Full Text PDFGaucher disease type 1 is a lysosomal storage disorder caused by mutations that reduce glucocerebrosidase activity, leading to glycolipid buildup, particularly in macrophages. To develop a curative approach, we established a high-efficiency genome editing platform for human and murine hematopoietic stem-progenitor cells using CRISPR/Cas9, recombinant adeno-associated virus serotype 6. To enhance homology-directed DNA repair while minimizing genotoxicity, we incorporated a new 53BP1 inhibitor, a ubiquitin variant that promotes DNA end resection and significantly increases editing efficiency.
View Article and Find Full Text PDFEur Heart J
August 2025
Translational Cardiology, Department of Cardiology and Department of Physiology, University Hospital Bern, University of Bern, Bern, Switzerland.
Background And Aims: Type 1 short QT syndrome (SQT1) is a genetic channelopathy caused by gain-of-function variants in KCNH2. This shortens cardiac repolarization and QT intervals, predisposing patients to ventricular arrhythmias and sudden cardiac death. This study aimed to investigate the therapeutic efficacy of KCNH2-specific suppression-and-replacement (KCNH2-SupRep) gene therapy in a transgenic rabbit model of SQT1.
View Article and Find Full Text PDFMol Ther
August 2025
RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Department of Molecular Medicine, University of Massachusetts Chan Medic
Alpha-1 antitrypsin deficiency (AATD) is commonly caused by a G-to-A mutation in the SERPINA1 gene (the PiZ mutation). The mutant PiZ AAT protein is sequestered in hepatocytes, causing lung emphysema due to insufficient AAT protein to inhibit neutrophil elastase in the lung. Here, we show that a compact adenine base editor (ABE) with an evolved Cas9 nickase derived from Neisseria meningitidis (eNme2.
View Article and Find Full Text PDFMed Microbiol Immunol
August 2025
Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.