Wang Yong, Yuan Fan
Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Ann Biomed Eng. 2006 Jan;34(1):114-27. doi: 10.1007/s10439-005-9007-2. Epub 2006 Mar 7.
It is a challenge to deliver therapeutic genes to tumor cells using viral vectors because (i) the size of these vectors are close to or larger than the space between fibers in extracellular matrix and (ii) viral proteins are potentially toxic in normal tissues. In general, gene delivery is hindered by various physiological barriers to virus transport from the site of injection to the nucleus of tumor cells and is limited by normal tissue tolerance of toxicity determined by local concentrations of transgene products and viral proteins. To illustrate the obstacles encountered in the delivery and yet limit the scope of discussion, this review focuses only on extracellular transport in solid tumors and distribution of viral vectors in normal organs after they are injected intravenously or intratumorally. This review also discusses current strategies for improving intratumoral transport and specificity of viral vectors.
使用病毒载体将治疗性基因递送至肿瘤细胞是一项挑战，原因如下：（i）这些载体的大小接近或大于细胞外基质中纤维之间的间距；（ii）病毒蛋白在正常组织中可能具有毒性。一般而言，基因递送受到多种生理屏障的阻碍，这些屏障影响病毒从注射部位转运至肿瘤细胞核，并且受到由转基因产物和病毒蛋白的局部浓度所决定的正常组织毒性耐受性的限制。为了说明递送过程中遇到的障碍并限制讨论范围，本综述仅关注实体瘤中的细胞外转运以及静脉内或瘤内注射后病毒载体在正常器官中的分布。本综述还讨论了改善病毒载体瘤内转运和特异性的当前策略。
