Delivering gene therapy for mucopolysaccharide diseases.
Delivering gene therapy for mucopolysaccharide diseases.
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DOI：
10.3389/fmolb.2022.965089
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
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作者：
粘多糖病是一组儿科遗传性溶酶体贮积病，由酶缺乏引起，导致全身糖胺聚糖（GAG）积聚。患者的寿命严重缩短，症状广泛，包括炎症、骨关节、心脏、呼吸和神经系统疾病。目前MPS疾病的治疗方法围绕两个主要策略。酶替代疗法（ERT）在治疗躯体症状方面是有效的，但其对神经功能的影响有限。造血干细胞移植（HSCT）具有通过单核细胞运输穿过BBB的潜力，然而递送的酶剂量几乎仅限制其用于MPSI Hurler。基因治疗是治疗MPS疾病的新兴治疗策略。在这篇综述中，我们将讨论用于MPS基因治疗的各种载体，以及一些正在进行临床前和临床开发的最新基因编辑方法。
Mucopolysaccharide diseases are a group of paediatric inherited lysosomal storage diseases that are caused by enzyme deficiencies, leading to a build-up of glycosaminoglycans (GAGs) throughout the body. Patients have severely shortened lifespans with a wide range of symptoms including inflammation, bone and joint, cardiac, respiratory and neurological disease. Current treatment approaches for MPS disorders revolve around two main strategies. Enzyme replacement therapy (ERT) is efficacious in treating somatic symptoms but its effect is limited for neurological functions. Haematopoietic stem cell transplant (HSCT) has the potential to cross the BBB through monocyte trafficking, however delivered enzyme doses limit its use almost exclusively to MPSI Hurler. Gene therapy is an emerging therapeutic strategy for the treatment of MPS disease. In this review, we will discuss the various vectors that are being utilised for gene therapy in MPS as well as some of the most recent gene-editing approaches undergoing pre-clinical and clinical development.