Specific targets in tumor tissue for the delivery of therapeutic genes.
Specific targets in tumor tissue for the delivery of therapeutic genes.
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DOI：
10.2174/1568011053174855
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发表时间：
2005-03-01
期刊：
影响因子：
--
通讯作者：
Ogris, Manfred
中科院分区：
文献类型：
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作者：
Gunther, Michael;Wagner, Ernst;Ogris, Manfred
基因治疗是分子医学一个不断发展的领域的一部分，它将在人类疾病的治疗中变得越来越重要。到目前为止，几乎三分之二的基因治疗临床试验是针对癌症的，因为超过一定尺寸的实体肿瘤依赖于血液供应，通过血流给药颗粒基因输送载体是一个很有前途的概念。肿瘤细胞和肿瘤血管系统都提供了特定的分子靶点，可用于治疗基因的定点传递。包括基因递送载体在内的大分子药物的被动靶向肿瘤可以通过所谓的增强通透性和保留率(EPR)效应来实现。当使用肿瘤靶向配体时，特异性可显著增强。通常对肿瘤组织没有自然趋向性的病毒载体被产生来在其表面携带肿瘤靶向分子。基于阳离子脂类或阳离子聚合物的合成基因传递载体被生化修饰，以结合肿瘤细胞或肿瘤血管的特异性配体。对于系统应用，这些传递系统必须满足一定的条件。传递载体不应引起任何免疫原性和炎症反应。已经进行了几项研究来降低病毒载体的免疫原性；对非病毒基因递送系统的表面修饰减少了它们与血液成分的非特异性相互作用。在基因水平上，肿瘤特异性启动子增加了额外的特异性层，限制转基因在肿瘤组织中的表达。这篇综述将包括针对肿瘤的颗粒基因转移载体的系统应用，并将对癌症基因治疗的治疗概念进行概述。
Gene therapy is part of a growing field in molecular medicine, which will gain importance in the treatment of human diseases. Until now, almost two thirds of all clinical trials performed in gene therapy are directed against Cancer As solid tumors exceeding a certain size rely on blood supply, the administration of particulate gene delivery vectors via the bloodstream is a promising concept. Tumor cells and the tumor vasculature both offer specific molecular targets, which can be utilized for the site directed delivery of therapeutic genes. Passive targeting of macromolecular drugs including gene delivery vectors to tumors can be achieved by the so called enhanced permeability and retention (EPR) effect. The specificity can be markedly enhanced when tumor targeting ligands are used. Viral vectors, which usually do not have a natural tropism for tumor tissue, were generated to carry tumor targeting molecules on their surface. Synthetic gene delivery vectors, based on cationic lipids or cationic polymers were biochemically modified to incorporate ligands specific for tumor cells or tumor vasculature. For systemic application, these delivery systems have to fulfill certain conditions. The delivery vector should not induce any immunogenic and inflammatory responses. Several studies were conducted to reduce the immunogenicity of viral vectors; surface modification of non-viral gene delivery systems reduced their non-specific interaction with blood components. On the genetic level, tumor specific promoters add additional layers of specificity restricting the transgene expression to the tumor tissue. This review will cover the systemic application of particulate gene transfer vectors targeted to tumors and will give an overview of therapeutic concepts for cancer gene therapy.