Abstract:

Primary immunodeficiency diseases are inherent disorders in which part of the immune system is missing or does not function normally. The incidence rate of PID is about 1/5000，and there are at least 200 000 survivors in China. The hematopoietic stem cell transplantation results in the recovery of the majority of the current lethal PID patients，but the majority of the children are unable to receive treatment because of lacking HLA-matched donor，high cost and varying degrees of immune rejection. Gene therapy refers to the repair of autologous hematopoietic stem cell mutations in patients to reconstruct the immune system. PID has always been the preferred disease for gene therapy，gene therapy is also the most promising PID cure strategy. Gene therapy has been succeeded in many kinds of the PID disease，and some PID centers in China have also started preclinical study. In addition，TALEN，ZFN，CRISPR-Cas9 technology，as the in-situ gene editing technology，have been studied deeply，so defective gene repair in situ is possible，and the problem of precise regulation of gene expression and maintaining genome integrity can be solved. All in all，gene therapy will benefit the PID children and families in the near future.

Key words: primary immunodeficiency , diseases；gene therapy；gene editing；vector

摘要：

原发性免疫缺陷病（PID）是由基因突变造成免疫细胞数量和（或）功能异常的一类致死性疾病， 发病率约1/5000，我国至少有存活患儿200 000例。造血干细胞移植为目前大部分致死性PID的惟一根治手段，但由于供者难寻、花费巨大以及不同程度的免疫排异反应，大部分患儿无法接受治疗。基因治疗指对患者自体造血干细胞突变基因进行修复，以重建免疫系统的新型根治方法。PID历来是基因治疗的首选适应证，基因治疗同样也是PID最具前景的新型根治手段，已经在许多PID病种中取得初步成功。我国部分单位也已启动PID基因治疗临床前研究。另外，以TALEN、ZFN、CRISPR-Cas9技术为代表的定点甚至原位基因编辑技术的深入研究，使缺陷基因原位修复成为可能，完全有希望解决基因表达精确调控、保持基因组完整性等难题，让基因治疗造福广大PID患儿及家庭。

关键词: 原发性免疫缺陷病, 基因治疗, 基因编辑, 载体