Department of Physiology, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Neuroscience Research Institute, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Cells. 2024 Jul 18;13(14):1214. doi: 10.3390/cells13141214.
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system continues to evolve, thereby enabling more precise detection and repair of mutagenesis. The development of CRISPR/Cas-based diagnosis holds promise for high-throughput, cost-effective, and portable nucleic acid screening and genetic disease diagnosis. In addition, advancements in transportation strategies such as adeno-associated virus (AAV), lentiviral vectors, nanoparticles, and virus-like vectors (VLPs) offer synergistic insights for gene therapeutics in vivo. Wilson's disease (WD), a copper metabolism disorder, is primarily caused by mutations in the ATPase copper transporting beta () gene. The condition is associated with the accumulation of copper in the body, leading to irreversible damage to various organs, including the liver, nervous system, kidneys, and eyes. However, the heterogeneous nature and individualized presentation of physical and neurological symptoms in WD patients pose significant challenges to accurate diagnosis. Furthermore, patients must consume copper-chelating medication throughout their lifetime. Herein, we provide a detailed description of WD and review the application of novel CRISPR-based strategies for its diagnosis and treatment, along with the challenges that need to be overcome.
成簇规律间隔短回文重复序列 (CRISPR)/CRISPR 相关蛋白 (Cas) 系统不断进化，从而能够更精确地检测和修复突变。基于 CRISPR/Cas 的诊断方法具有高通量、经济高效和便携的核酸筛选和遗传疾病诊断的潜力。此外，腺相关病毒 (AAV)、慢病毒载体、纳米颗粒和类病毒载体 (VLPs) 等运输策略的进步为体内基因治疗提供了协同见解。肝豆状核变性 (WD) 是一种铜代谢紊乱疾病，主要由 ATP 酶铜转运β (ATP7B) 基因的突变引起。这种情况与体内铜的积累有关，导致包括肝脏、神经系统、肾脏和眼睛在内的各种器官的不可逆转损伤。然而，WD 患者的身体和神经症状的异质性和个体表现对准确诊断构成了重大挑战。此外，患者必须终生服用铜螯合剂药物。本文详细描述了 WD，并回顾了新型基于 CRISPR 的策略在其诊断和治疗中的应用，以及需要克服的挑战。
