Phillips M Ian, Tang Yao Liang
Keck Graduate Institute, Claremont, Ca 91711, USA.
Adv Drug Deliv Rev. 2008 Jan 14;60(2):160-72. doi: 10.1016/j.addr.2007.08.035. Epub 2007 Oct 11.
Gene modification of cells prior to their transplantation, especially stem cells, enhances their survival and increases their function in cell therapy. Like the Trojan horse, the gene-modified cell has to gain entrance inside the host's walls and survive and deliver its transgene products. Using cellular, molecular and gene manipulation techniques the transplanted cell can be protected in a hostile environment from immune rejection, inflammation, hypoxia and apoptosis. Genetic engineering to modify cells involves constructing modules of functional gene sequences. They can be simple reporter genes or complex cassettes with gene switches, cell specific promoters and multiple transgenes. We discuss methods to deliver and construct gene cassettes with viral and non-viral delivery, siRNA, and conditional Cre/Lox P. We review the current uses of gene-modified stem cells in cardiovascular disease, diabetes, neurological diseases, (including Parkinson's, Alzheimer's and spinal cord injury repair), bone defects, hemophilia, and cancer.
细胞在移植前进行基因改造，尤其是干细胞，可提高其在细胞治疗中的存活率并增强其功能。基因改造后的细胞就像特洛伊木马一样，必须进入宿主内部并存活下来，然后传递其转基因产物。通过细胞、分子和基因操作技术，移植的细胞可以在恶劣环境中免受免疫排斥、炎症、缺氧和凋亡的影响。对细胞进行基因工程改造涉及构建功能基因序列模块。它们可以是简单的报告基因，也可以是带有基因开关、细胞特异性启动子和多个转基因的复杂盒式结构。我们将讨论使用病毒和非病毒递送、小干扰RNA（siRNA）以及条件性Cre/Lox P来递送和构建基因盒式结构的方法。我们还将综述基因改造干细胞在心血管疾病、糖尿病、神经疾病（包括帕金森病、阿尔茨海默病和脊髓损伤修复）、骨缺损、血友病和癌症中的当前应用。
