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Correcting a pathogenic mitochondrial DNA mutation by base editing in mice.
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Graduate Program in Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue (M-860), Miami, FL 33136, USA.
Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.
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Altered protein conformation can cause incurable neurodegenerative disorders. Mutations in , the gene encoding neuroserpin, can alter protein conformation resulting in cytotoxic aggregation leading to neuronal death. Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare autosomal dominant progressive myoclonic epilepsy that progresses to dementia and premature death.
View Article and Find Full Text PDFModulating gene expression as a strategy to investigate thyroid cancer biology.
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Modulating the expression of a coding or noncoding gene is a key tool in scientific research. This strategy has evolved methodologically due to advances in cloning approaches, modeling/algorithms in short hairpin RNA (shRNA) design for knockdown efficiency, and biochemical modifications in RNA synthesis, among other developments. Overall, these modifications have improved the ways to either reduce or induce the expression of a given gene with efficiency and facility for implementation in the lab.
View Article and Find Full Text PDFThe C-terminal structure of the N6-methyladenosine deaminase YerA and its role in deamination.
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The N6-methyladenine (6mA) modification is an essential epigenetic marker and plays a crucial role in processes, such as DNA repair, replication, gene expression regulation, etc. YerA from Bacillus subtilis is considered a novel class of enzymes capable of catalyzing the deamination of 6mA to produce hypoxanthine. Despite the significance of this type of enzymes in bacterial self-defense systems and potential applications as a gene-editing tool, the substrate specificity, the catalytic mechanism and the physiological function of YerA are currently unclear due to the lack of structural information.
View Article and Find Full Text PDFInfectious diseases pose significant challenges to Norwegian Atlantic salmon aquaculture. Vaccines are critical for disease prevention; however, a deeper understanding of the immune system is essential to improve vaccine efficacy. Immunoglobulin M (IgM) is the main antibody involved in the systemic immune response of teleosts, including Atlantic salmon.
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