Understanding and treating kidney disease in arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome

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Chronic Kidney Disease (CKD) affects 1 in 10 adults and costs the NHS approximately £1.45 billion annually. Some cases of CKD are due to genetic mutations which affect the biology of kidney tubular epithelial cells or podocytes of the kidney filtration barrier, resulting in a loss of kidney function and patients requiring dialysis or transplantation. Gene therapy could provide a potential solution for these cases of CKD. However, there has been limited success transducing podocytes or tubular epithelial cells with adeno-associated viruses (AAVs) in vivo. This project aims to address this by identifying new AAVs which can successfully transduce kidney cells. This will be done using a kit which allows us to screen 70 AAV different serotypes simultaneously and identify those which transduce kidney cells most effectively. The AAVs will be screened both in monolayer cultures, kidney organoids and in-vivo to determine both their physical and functional transduction efficacies. Once screened, the most effective AAVs will be used as vectors to correct a genetic mutation in both in vivo and in vitro disease models of genetic renal diseases such as arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome.