"liver transplantation is an effective therapy for end-stage liver disease. But the transplantation rejective response is a formidable problem after liver transplantation, especially acute rejection which is the main cause of early dysfunction and transplantation failure [7]. The incidence rate of acute rejection after liver transplantation is up to 50% to 70% [8]. The acute rejection after the organ transplantation is mainly caused by the activation of the immune system in the host. During the acute rejection, T cells are the most important effectors involved in antigen recognition, lymphcyte proliferation and differentiation, and immune regulation, cytolysis. 4-1BB plays a critical role in allograft rejection"
"RNAi-based gene silencing is more rapid and cost-effective compared with the gene knockout techniques. RNA interference (RNAi) is a powerful tool to induce loss-of-function phenotypes by posttranscriptional silencing of gene expression. Viral delivery of short hairpin RNA (shRNA) expression cassettes allows efficient transduction in tissues such as immunological cell in vivo [29]. The knockdown of gene expression has been achieved using lentiviral vector constructs that express shRNAs within vector-infected cells. The lentiviral vector system provided useful tools for elucidating gene function by analysis of loss-of-function phenotypes and for exploring the application of RNAi in gene therapy [30]. In our study, The recombination vector of lentivirus containing shRNA targeting the 4-1BB gene was successfully constructed. The liver transplantation was performed using the two-cuff technique. BN recipient rats were infected by the recombinant LVs. The results showed that gene silencing of 4-1BB by RNA interference downregulated the 4-1BB gene expression of the splenic lymphocytes isolated from the recipient rats with liver transplantation. Our results also showed that lentivirus-mediated delivery of shRNA targeting 4-1BB gene prolonged the survival time of recipient rats. These results suggested that the silencing of 4-1BB gene by RNA interference was successful in the recipient rats and useful for the liver transplantation"
"In conclusion, we have demonstrated that gene silencing of 4-1BB by RNA interference inhibits the acute rejection in rats with liver transplantation and it is a promising strategy to prevent progression of graft rejection"
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