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Stable transduction of the neonatal mouse liver using a hybrid rAAV/sleeping beauty transposon gene delivery system.
J Gene Med
August 2024
Gene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW, Australia.
Background: Conventional adeno-associated viral (AAV) vectors, while highly effective in quiescent cells such as hepatocytes in the adult liver, confer less durable transgene expression in proliferating cells owing to episome loss. Sustained therapeutic success is therefore less likely in liver disorders requiring early intervention. We have previously developed a hybrid, dual virion approach, recombinant AAV (rAAV)/piggyBac transposon system capable of achieving stable gene transfer in proliferating hepatocytes at levels many fold above conventional AAV vectors.
View Article and Find Full Text PDFUnraveling cysteine deficiency-associated rapid weight loss.
bioRxiv
July 2024
Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Forty percent of the US population and 1 in 6 individuals worldwide are obese, and the incidence of this disease is surging globally. Various dietary interventions, including carbohydrate and fat restriction, and more recently amino acid restriction, have been explored to combat this epidemic. We sought to investigate the impact of removing individual amino acids on the weight profiles of mice.
View Article and Find Full Text PDFIntroduction: Lysinuric protein intolerance (LPI) is a rare inherited metabolic disease. It is caused by a deficiency in cationic amino acid transport caused by mutations in SLC7A7 gene.
Aim: To identify the clinical, diagnostic and therapeutic features of lysnuric protein intolerance.
The Strange Case of Orotic Acid: The Different Expression of Pyrimidines Biosynthesis in Healthy Males and Females.
J Pers Med
September 2023
Laboratory of Clinical Pharmacology "Franco Ghezzo", Department of Clinical and Biological Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043 Turin, Italy.
Orotic acid (OA) is an intermediate metabolite of pyrimidine nucleotide biosynthesis and represents a minor diet constituent. The measurement of urinary orotic acid is useful in confirming the diagnosis of hereditary metabolic diseases. Moreover, it could be of interest to know how the physiological concentration of this metabolite changes in relation to different conditions of clinical normality.
View Article and Find Full Text PDFRenal function, sex and age influence purines and pyrimidines in urine and could lead to diagnostic misinterpretation.
Mol Genet Metab
November 2023
Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Glomerular filtration rate (GFR) is commonly used in clinical practice for the diagnosis and follow-up of chronic kidney disease. Screening for inborn errors of metabolism (IEM) is based on analysis of biomarkers in urine, reported by their ratio to urinary creatinine (crn). Impaired renal function may complicate the interpretation of several biomarkers used for screening of IEM.
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