ABSTRACT

Introduction

Primary immunodeficiencies (PIDs) are monogenic disorders of the immune system associated with increased susceptibility to life-threatening infection. Curative treatment has been limited to hematopoietic stem cell transplant (HSCT), however toxic immunosuppression, graft failure, and graft versus host disease greatly reduce overall survival rates. Gene therapy is a targeted curative therapy that reduces these risks by utilizing autologous hematopoietic stem cells. The treatment has found significant success and is anticipated to become the standard of care in a number of PIDs.

Areas covered

This review is a summary of the developments in gene therapy, gene editing, and current gene therapy approaches in specific PIDs.

Expert opinion

The field of gene therapy has rapidly developed over the last three decades, with the first licensed pharmaceutical gene therapy product now available. After initial clinical trials discovered serious adverse events in the form of insertional oncogenesis, significant improvements in vector design have made the treatment a viable curative therapy. Cryopreservation has expanded the scope of gene therapy by increasing accessibility of the product to wider geographic locations. Targeted gene editing using engineered nucleases, while still in early stages of development, will further add to the repertoire of potential treatments available for PIDs.

中文翻译：

---

原发性免疫缺陷的基因治疗：最新

摘要

介绍

原发性免疫缺陷 (PID) 是免疫系统的单基因疾病，与对威胁生命的感染的易感性增加有关。治愈性治疗仅限于造血干细胞移植 (HSCT)，但是毒性免疫抑制、移植失败和移植物抗宿主病会大大降低总生存率。基因疗法是一种靶向治疗，通过利用自体造血干细胞降低这些风险。该治疗已取得重大成功，预计将成为许多 PID 的护理标准。

覆盖区域

这篇综述总结了基因治疗、基因编辑和特定 PID 中当前基因治疗方法的发展。

专家意见

在过去的三十年中，基因治疗领域发展迅速，第一个获得许可的药物基因治疗产品现已上市。在最初的临床试验发现插入性肿瘤形成形式的严重不良事件后，载体设计的显着改进使该治疗成为可行的治愈性疗法。冷冻保存通过增加产品在更广泛地区的可及性，扩大了基因治疗的范围。使用工程化核酸酶进行靶向基因编辑，虽然仍处于开发的早期阶段，但将进一步增加可用于 PID 的潜在治疗方案。