LIPOSOME-MEDIATED GENE-TRANSFER AND EXPRESSION VIA THE SKIN
LIPOSOME-MEDIATED GENE-TRANSFER AND EXPRESSION VIA THE SKIN
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DOI：
10.1093/hmg/4.12.2279
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发表时间：
1995-12-01
影响因子：
3.5
通讯作者：
AKHURST, RJ
中科院分区：
文献类型：
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作者：
ALEXANDER, MY;AKHURST, RJ
使用β-半乳糖苷酶基因表达构建体来研究当DNA/脂质体复合物局部应用于小鼠体内皮肤时基因递送和表达的有效性。将DNA与N-[1-（2，3-二油酰氧基）丙基]-N，N，N-三甲基-铵甲基-硫酸盐（DOTAP）的商业制剂以1：1.6（w/w）的比例复合。DNA迅速穿透皮肤并在表皮、真皮和毛囊中表达。发现267 μ g/ml DNA的DNA浓度对于有效转染是最佳的。早在应用后6小时就看到表达，在处理后24和48小时持续高水平，但在应用后7天显著降低。总之，利用市售脂质体制剂，局部应用的DNA/脂质体复合物可以在皮肤内的几种细胞类型中有效地递送和表达。这种简单的非侵入性技术可能对许多基因治疗应用产生影响。
A beta-galactosidase gene expression construct was used to investigate the effectiveness of gene delivery and expression when DNA/liposome complexes were topically applied to mouse skin in vivo. DNA was complexed with a commercial preparation of N-[1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethyl-ammoniummethyl-sulphate (DOTAP) in a ratio of 1:1.6 (w/w). The DNA rapidly penetrated the skin and was expressed in the epidermis, dermis and hair follicles. A DNA concentration of 267 mu g/ml DNA was found to be optimal for efficient transfection. Expression was seen as early as 6 h post-application, persisted at high levels 24 and 48 h post-treatment, but was markedly reduced by 7 days after application. In conclusion, utilising a commercially available liposome preparation, topically-applied DNA/liposome complexes can be efficiently delivered and expressed in several cell types within the skin. This simple, non-invasive technique may have implications for a number of gene therapy applications.