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

了解和治疗关节弯曲-肾功能障碍-胆汁淤积 (ARC) 综合征中的肾脏疾病

• 批准号: 2396509
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2396509
• 关键词: Understanding; treating; kidney; disease; arthrogryposis

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.

慢性肾脏病（CKD）影响十分之一的成年人，每年花费NHS约14.5亿英镑。一些CKD病例是由于影响肾小管上皮细胞或肾滤过屏障足细胞生物学的基因突变，导致肾功能丧失和需要透析或移植的患者。基因治疗可以为这些CKD病例提供潜在的解决方案。然而，在体内用腺相关病毒（AAV）转导足细胞或肾小管上皮细胞的成功有限。该项目旨在通过识别可以成功地使肾细胞增殖的新的AAV来解决这个问题。这将使用试剂盒完成，该试剂盒允许我们同时筛选70种AAV不同血清型并鉴定最有效地抑制肾细胞的那些。将在单层培养物、肾类器官和体内筛选AAV，以确定其物理和功能转导功效。一旦筛选，最有效的AAV将用作载体，以校正遗传性肾病（如关节弯曲-肾功能障碍-胆汁淤积（ARC）综合征）的体内和体外疾病模型中的遗传突变。