Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer
Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer
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DOI：
10.1038/nmat1524
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发表时间：
2005-12-01
期刊：
影响因子：
41.2
通讯作者：
Kataoka, K
中科院分区：
文献类型：
--
作者：
Nishiyama, N;Iriyama, A;Kataoka, K
体内基因转染的控制是基因治疗的核心问题。光化学内化是一种允许光诱导DNA、药物或其他生物因子直接进入细胞的技术。通常需要在给药系统中加入光敏剂来光化学破坏内体膜的稳定性。在这里，我们提出了一种体内DNA递送系统，其中这两种成分被组装成一个结构。这是一种三元配合物，由一个含有DNA的核心组成，该核心被阳离子肽包裹，并被阴离子树状大分子酞菁包裹，酞菁提供光敏作用。该三元配合物在体外表现出100倍以上的转基因表达增强光化学作用，并降低了光细胞毒性。在动物实验中，在激光照射后皮下注射三元配合物导致转基因仅在激光照射部位表达。这项工作展示了树状大分子在生物医学上的新应用，并首次成功地在光化学内化介导的基因在体内传递。
The control of gene transfection in the body is a core issue in gene therapy. Photochemical internalization is a technology that allows light-induced delivery of DNA, drugs or other biological factors directly inside cells. Usually it requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. Here we present a system for in vivo DNA delivery in which these two components are assembled into one structure. This is a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer phthalocyanine, which provides the photosensitizing action. The ternary complex showed more than 100-fold photochemical enhancement of transgene expression in vitro with reduced photocytotoxicity. In an animal experiment, subconjuctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site. This work demonstrates a new biomedical application for dendrimers, and the first success in the photochemical-internalization-mediated gene delivery in vivo.