Hengge U R, Walker P S, Vogel J C
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Invest. 1996 Jun 15;97(12):2911-6. doi: 10.1172/JCI118750.
The insertion and expression of genes in the epidermis may have a variety of therapeutic uses, including the treatment of skin diseases. Here we show that when both human skin organ cultures and human skin grafts on immunocompromised mice are injected with naked DNA, the DNA is taken-up and genes are expressed in the epidermis in a manner similar to both pig skin injected in vivo and injected pig skin organ cultures. In contrast, DNA injected into mouse skin is expressed not just in the epidermis, but also in the dermis and underlying fat and muscle tissue, and is expressed at lower levels. These findings suggest that genes can be expressed in human skin, after injection of naked DNA, and indicate that pig skin is an appropriate model for the study of DNA uptake and gene expression in human skin. The organ cultures of human and pig skin may be useful in understanding how naked DNA is internalized and expressed after in vivo injections. Additionally, skin obtained from patients with skin disease may be studied as skin grafts and organ cultures to help optimize genetic approaches for the treatment of skin diseases prior to clinical trials, by determining if the injected gene can provide a therapeutic benefit.
基因在表皮中的导入和表达可能具有多种治疗用途，包括治疗皮肤疾病。我们在此表明，当向人皮肤器官培养物以及免疫功能低下小鼠身上的人皮肤移植物注射裸DNA时，DNA会被摄取，并且基因会在表皮中表达，其方式类似于体内注射的猪皮肤以及注射后的猪皮肤器官培养物。相比之下，注入小鼠皮肤的DNA不仅在表皮中表达，还在真皮以及下方的脂肪和肌肉组织中表达，且表达水平较低。这些发现表明，注射裸DNA后基因可在人皮肤中表达，并表明猪皮肤是研究人皮肤中DNA摄取和基因表达的合适模型。人和猪皮肤的器官培养物可能有助于理解体内注射后裸DNA是如何内化和表达的。此外，从皮肤病患者身上获取的皮肤可作为皮肤移植物和器官培养物进行研究，通过确定注入的基因是否能提供治疗益处，来帮助在临床试验前优化治疗皮肤病的基因方法。
