脊髓性肌萎缩症（spinal muscular atrophy，SMA）是一种常染色体隐性遗传病，是由于SMN1基因的纯合性缺失、突变以及截断，导致脊髓前角运动神经元退行性病变。据统计，大约有98.7%的SMA患者是SMN1基因的7号外显子缺失甚至7、8号外显子同时缺失，同时SMA也是导致婴幼儿死亡的第一大遗传性疾病。其发病率为1/6000～1/10000，携带率为1/40～1/50。目前，SMA无有效的治疗方法。基因治疗为类似SMA这样的严重单基因遗传病带来了新的治疗方式，但常规的添加SMN1基因或利用SMN2替代SMN1的基因治疗方法并不理想。由此我们提出一种针对SMN1基因的原位修复策略，即通过基因打靶将SMN1基因中缺失的7、8号外显子原位添加进去。联合我们已建立的iPSC技术、干细胞基因打靶技术以及TALEN技术，我们希望能够为SMA提供有效的基因治疗方案。

Spinal muscular atrophy (SMA), which is a common neuromuscular disorder with autosomal recessive inheritance, resulting in the degeneration of motor neurons, is caused by homozygous deletion, truncation, mutation or gene conversion of survival motor neuron 1(SMN1). Then approximately 98.7% in patients is the deletion of the SMN1 gene in exon 7 or even in exon 7 and exon 8. SMA is the first substantial genetic diseases of infant death. The estimated incidence is 1 in 6000～10,000 newborns with a carrier frequency of 1 in 40～60. At present, SMA no effective treatment. Gene therapy has brought about a new way therapy for severe monogenic disease similar to SMA. It is not an ideal approach that through add SMN1 gene or using SMN2 instead of SMN1. We highlight in situ remediation strategies for SMN1 gene, in situ added the SMN1 gene in exon 7, 8 by gene targeting. Combine with, we had established, iPSC technology, stem cell gene targeting technology and TALEN technology, we hope to establish an effective therapy for SMA.