Reconstituting retroviral (ReCon) vectors facilitating delivery of cytotoxic genes in cancer gene therapy approaches

摘要: Background We have previously described the generation of reconstituting retroviral (ReCon) vectors designed for cancer gene therapy using cytotoxic products. The unique vector structure with a promoter physically separated from transgene allows stable virus producer cells irrespective toxic gene. mechanism synthesis DNA RNA dictates that infection leads to reconstitution functional expression cassettes in target cell. Methods To improve titres, cytomegalovirus enhancer was inserted upstream 5′-long-terminal repeat (LTR); Woodchuck hepatitis post-transcriptional regulatory element and an elongated attachment site 3′-LTR were included. In addition, bacterial origin replication deleted internal polyadenylation signal mutated. Transcriptional targeting attempted by introducing mammary tissue-specific promoters such as U3 region mouse tumour or whey acidic protein encoding All modifications analysed detail respect production infectivity. Finally, armed λ-holin transduced effects. Results Distinct resulted titre improvement more than 560-fold. Compatibility optimized targeted cellular demonstrated. When equipped gene, could be successfully established high rigorous cell killing. Conclusions The ReCon its form is attractive tool approaches. Copyright © 2007 John Wiley & Sons, Ltd.