Receptor-mediated Liver-specific Transfer Of Herpes Simplex Virus Tymidine Kinase Gene In Vitro And In Vivo

Successful gene therapy relies on safe and efficient gene transfer methods and high level expression of foreign gene. Ideal gene transfer vector would be safe, targetable, in vivo useful and so on. Among the gene transfer vectors currently available, viral vectors are more perfect. But their utility range is limited as they lack gene transfer targeting and are dangerous with some degree. Non-viral vectors, as relative safe, especially receptor-mediated pathway with targeting gene transfer, have been emphosized recently. Some studies have demonstrated that freereplication-defective adenovirus(Ad) or modified adenovirus(Ad-PLL) could result in the efficiency of receptor-mediated gene transfer as high as 100%. However, molecular conjugate vector containing adenovirus could enter cells via adenovirus receptor which exists on large range type of cell membrane, its cell targeting is affected. To solve this problem, we consider that use of tissue-specific regulative elements in construction of plasmid vector for molecular conjugate vector may limit the expression of foreign gene to targeting cells further. In this case, targeting of gene transfer would be enhanced and high level of gene expression could beachievedIn our study, adenovirus enhanced, asialoorosomusoid (ASOR) receptor - mediated gene transfer method was employed for liver-directed gene transfer. In construction of eukaryotic expressing plasmid vector, herpes simplex virus thymidine kinase(HSV-TK) gene was set under the control of human albumin (ALB) gene promoter / enhancer or...