ABSTRACT

Introduction

Inborn errors of metabolism include several genetic disorders due to disruption of cellular biochemical reactions. Although individually rare, collectively they are a large and heterogenous group of diseases affecting a significant proportion of patients. Available treatments are often unsatisfactory. Liver-directed gene therapy has potential for treatment of several inborn errors of metabolism. While lentiviral vectors and lipid nanoparticle-mRNA have shown attractive features in preclinical studies and still have to be investigated in humans, adeno-associated virus (AAV) vectors have shown clinical success in both preclinical and clinical trials for in vivo liver-directed gene therapy.

Areas covered

In this review, we discussed the most relevant clinical applications and the challenges of liver-directed gene-based approaches for therapy of inborn errors of metabolism.

Expert Opinion

Challenges and prospects of clinical gene therapy trials and preclinical studies that are believed to have the greatest potential for clinical translation are presented.

中文翻译：

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先天性代谢障碍的肝脏导向基因疗法

摘要

介绍

先天性代谢错误包括由于细胞生化反应中断引起的几种遗传疾病。尽管个别罕见，但总的来说，它们是影响相当大比例患者的一大群异质疾病。现有的治疗方法往往不尽如人意。肝脏导向基因疗法具有治疗多种先天性代谢缺陷的潜力。虽然慢病毒载体和脂质纳米颗粒-mRNA 在临床前研究中显示出有吸引力的特征并且仍需在人体中进行研究，但腺相关病毒 (AAV) 载体已在体内肝脏导向基因治疗的临床前和临床试验中显示出临床成功.

覆盖区域

在这篇综述中，我们讨论了最相关的临床应用和基于肝脏的基因方法治疗先天性代谢缺陷的挑战。

专家意见

介绍了被认为具有最大临床转化潜力的临床基因治疗试验和临床前研究的挑战和前景。