Akporiaye E T, Hersh E
Department of Microbiology and Immunology University of Arizona, Tucson 85724, USA.
Curr Opin Mol Ther. 1999 Aug;1(4):443-53.
One of the major obstacles to the development of gene therapy for cancer is our inability to deliver genes to all targets within the body. Thus, effective methodology does not exist to deliver a gene intravenously with the expectation that it will selectively localize within the target tumor, will not localize in other tissues and will be expressed efficiently. While one can take advantage of tissue-specific promoters to activate the gene only in a given target tissue, only a small fraction of the vector will be taken up in the target tissue and expressed. Consequently, since accessible local or regional tumor masses are a major problem in many cancers, there has been a strong emphasis on clinical trials in intratumoral and peritumoral gene delivery.
癌症基因治疗发展的主要障碍之一是我们无法将基因递送至体内所有靶点。因此,不存在有效的方法可以静脉注射基因,并期望其能选择性地定位于靶肿瘤内,而不在其他组织中定位并高效表达。虽然可以利用组织特异性启动子仅在特定靶组织中激活基因,但只有一小部分载体能被靶组织摄取并表达。因此,鉴于在许多癌症中,可触及的局部或区域肿瘤块是一个主要问题,人们一直非常重视瘤内和瘤周基因递送的临床试验。