Efficient nonviral cutaneous transfection

Efficient nonviral cutaneous transfection
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DOI:
10.1006/mthe.2000.0107
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发表时间:
2000-08-01
期刊:
影响因子:
12.4
通讯作者:
Malone, RW
Malone, RW
中科院分区:
医学1区
文献类型:
--
作者:
Glasspool-Malone, J;Somiari, S;Malone, RW

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已经进行了旨在增强非病毒转基因递送至皮肤的啮齿动物、猪和灵长类动物的临床前体内实验。这些研究已经鉴定了一种化合物(金精三羧酸或ATA),其增强“裸”质粒和脉冲电场(电穿孔或EP)的转染活性,协同地将转基因表达提高到比用游离DNA观察到的平均高115倍(P < 0.00009)。当在有或没有ATA的情况下皮内注射质粒时,转染的细胞通常仅限于表皮。然而,当在相同注射后加入电穿孔时,真皮和皮下组织内大量的脂肪细胞和成纤维细胞以及大量的树突状细胞被转染。这一进展为皮肤基因治疗和核酸疫苗的开发创造了新的机会。
Preclinical in vivo rodent, porcine, and primate experiments aimed at enhancing nonviral transgene delivery to skin have been performed. These investigations have identified a compound (aurintricarboxylic acid or ATA) that enhances transfection activity of "naked" plasmid and pulsed electrical fields (electroporation or EP) that synergistically boosts transgene expression to an average of 115-fold more than that observed with free DNA (P < 0.00009). When plasmid is intradermally injected with or without ATA, the transfected cells are typically restricted to the epidermis. However, when electroporation is added after the same injection, larger numbers of adipocytes and fibroblasts and numerous dendritic-like cells within the dermis and subdermal tissues are transfected. This advance creates new opportunities for cutaneous gene therapy and nucleic acid vaccine development.