Abstract：
Inborn errors of immunity (IEI) present a unique paradigm in the realm of gene therapy, emphasizing the need for precision in therapeutic design. As gene therapy transitions from broad-spectrum gene addition to careful modification of specific genes, the enduring safety and effectiveness of these therapies in clinical settings have become crucial. This review discusses the significance of IEIs as foundational models for pioneering and refining precision medicine. We explore the capabilities of gene addition and gene correction platforms in modifying the DNA sequence of primary cells tailored for IEIs. The review uses four specific IEIs to highlight key issues in gene therapy strategies: X-linked agammaglobulinemia (XLA), X-linked chronic granulomatous disease (X-CGD), X-linked hyper IgM syndrome (XHIGM), and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX). We detail the regulatory intricacies and therapeutic innovations for each disorder, incorporating insights from relevant clinical trials. For most IEIs, regulated expression is a vital aspect of the underlying biology, and we discuss the importance of endogenous regulation in developing gene therapy strategies.
摘要：
先天性免疫错误（IEI）在基因治疗领域提出了独特的范式，强调治疗设计的精确性。随着基因治疗从广谱基因添加过渡到对特定基因的仔细修饰，这些疗法在临床环境中的持久安全性和有效性已变得至关重要.这篇综述讨论了IEI作为开拓和完善精准医学的基础模型的重要性。我们探索了基因添加和基因校正平台在修改为IEI定制的原代细胞的DNA序列方面的能力。该综述使用四个特定的IEI来强调基因治疗策略中的关键问题：X连锁无丙种球蛋白血症（XLA），X连锁慢性肉芽肿病（X-CGD），X连锁高IgM综合征（XHIGM），和免疫失调，多内分泌病,肠病,X连接（IPEX）。我们详细介绍了每种疾病的监管复杂性和治疗创新，纳入相关临床试验的见解。对于大多数IEI来说，调节表达是潜在生物学的一个重要方面，我们讨论了内源性调节在开发基因治疗策略中的重要性。
