In utero gene transfer into the pulmonary epithelium.
In utero gene transfer into the pulmonary epithelium.
复制标题
在子宫内基因转移到肺上皮中。
DOI：
10.1038/nm1195-1201
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发表时间：
1995
期刊：
影响因子：
82.9
通讯作者：
Larson,JE
中科院分区：
文献类型：
--
作者：
Sekhon,HS;Larson,JE
在妊娠早期，肺内表面结构简单，是体细胞基因转移的理想目标1 - 3。将基因转移到生长中的肺中，对于囊性纤维化的产前矫正尤其有用，囊性纤维化具有毁灭性的肺部并发症。此外，子宫内基因疗法有可能使个体免疫耐受，从而避免当前一代腺病毒载体所出现的免疫反应。我们在妊娠第16天将含有acz报告基因（Ad5.CMVlacZ）的复制缺陷腺病毒载体注射到大鼠幼崽的羊水中6 - 9。在妊娠第16天，大鼠肺的成熟度与22周的人类胎儿相当，因为它们的气道内衬着未分化的多能干细胞。幼崽在出生后一周（感染后13天）的气道中显示出高水平的报告基因表达。当肺体积增加约20倍，肺泡形成，上皮细胞分化2,3时，表达保持不变。这些数据表明，基因靶向未分化胎儿细胞是一种有效的基因治疗手段。
In early gestation the internal surface of the lung is structurally simple and an ideal target for somatic gene transfer1–3. The transfer of genes into the growing lung would be particularly useful in the prenatal correction of cystic fibrosis, which has devastating pulmonary complications. In addition,in uterogene therapy has the potential to immunotolerize the individual, and thereby to avoid the immune reactions now seen with the current generation of adenoviral vectors4,5. We injected a replication-defective adenoviral vector containing thelacZreporter gene (Ad5.CMVlacZ) into the amniotic fluid of rat pups on the 16th day of gestation6–9. At 16 days of gestation, rat lungs are equivalent in maturity to those of a 22-week human fetus as their airways are lined with undifferentiated multipotential stem cells. The pups showed high-level reporter gene expression in their airways a week following birth (13 days following infection). The expression was maintained during a time when the lung volume increased approximately 20-fold, alveolarization occurred, and the epithelial cells differentiated2,3. These data establish gene targeting of undifferentiated fetal cells as an effective means of gene therapy.