Multiple and time-scheduled in situ DNA delivery mediated by β-cyclodextrin embedded in a polyelectrolyte multilayer
Multiple and time-scheduled in situ DNA delivery mediated by β-cyclodextrin embedded in a polyelectrolyte multilayer
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DOI：
10.1073/pnas.0508246103
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发表时间：
2006-06-06
影响因子：
11.1
通讯作者：
Voegel, JC
中科院分区：
文献类型：
--
作者：
Jessel, N;Oulad-Abdeighani, M;Voegel, JC
基因治疗的基本前提是基因可用于原位产生治疗性蛋白质。生物材料中 DNA 复合物的受控递送提供了通过在细胞微环境中维持较高浓度的 DNA 来增强基因转移的潜力。将 DNA 固定到细胞粘附的基质上，可将 DNA 维持在细胞微环境中，以供随后的细胞内化。在这里，在带电环糊精的存在下构建了由含有 DNA 的聚（L-谷氨酸）（PLGA）和聚（L-赖氨酸）（PLL）制成的层层（LBL）薄膜。通过与膜接触的细胞在细胞核或细胞质中诱导产生特定蛋白质来测试这些聚电解质膜的生物活性。这种类型的涂层提供了同时或顺序界面递送不同 DNA 分子以进行细胞转染的可能性。例如，这些结果为贴片疫苗接种等众多潜在应用开辟了道路。
The basic premise of gene therapy is that genes can be used to produce in situ therapeutic proteins. The controlled delivery of DNA complexes from biornaterials offers the potential to enhance gene transfer by maintaining an elevated concentration of DNA within the cellular microenvironment. Immobilization of the DNA to the substrate to which cells adhere maintains the DNA in the cell microenvironment for subsequent cellular internalization. Here, layer-by-layer (LBL) films made from poly(L-glutamic acid) (PLGA) and poly(L-lysine) (PLL) containing DNA were built in the presence of charged cyclodextrins. The biological activities of these polyelectrolyte films were tested by means of induced production of a specific protein in the nucleus or in the cytoplasm by cells in contact with the films. This type of coating offers the possibility for either simultaneous or sequential interfacial delivery of different DNA molecules aimed at cell transfection. These results open the route to numerous potential applications in patch vaccination, for example.