tailieunhanh - Báo cáo y học: " Construction of Metabolically Biotinylated Adenovirus with Deleted Fiber Knob as Targeting Vector"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Construction of Metabolically Biotinylated Adenovirus with Deleted Fiber Knob as Targeting Vector | Liu et al. Virology Journal 2010 7 316 http content 7 1 316 VIROLOGY JOURNAL SHORT REPORT Open Access Construction of Metabolically Biotinylated Adenovirus with Deleted Fiber Knob as Targeting Vector Yanzheng Liu Philippe Valadon Jan E Schnitzer Abstract Gene delivery vectors based on adenovirus particularly human adenovirus serotype 5 hAd5 have great potential for the treatment of variety of diseases. However the tropism of hAd5 needs to be modified to achieve tissue- or cell- specific therapies for the successful application of this vector system to clinic. Here we modified hAd5 tropism by replacing the fiber knob which contains the coxsackievirus B and adenovirus receptor CAR -binding sites with a biotin acceptor peptide a truncated form of Propionibacterium shermanii S transcarboxylase domain PSTCD to enable metabolically biotinylation of the virus. We demonstrate here that the new adenovirus no longer shows CAR-dependent cell uptake and transduction. When metabolically biotinylated and avidin-coated it forms a nanocomplex that can be retargeted to distinct cells using biotinylated antibodies. This vector may prove useful in the path towards achieving targeted gene delivery. Findings The hAd5-based vector remains one of the most popular vector systems for gene delivery and cancer gene therapy. However the ubiquitous expression of adenoviral primary receptor CAR in many tissues and the predominant liver tropism of the vector after systemic administration limit the application of hAd5 vector to clinical use 1 . Therefore strategies to re-direct hAd5 infection and to decrease the rapid uptake of the virus by the reticuloendothelial system RES will be essential for many gene therapy applications. The hAd5 binds to most cell types through the interaction of its fiber knob domain with cell surface CAR 2 . Retargeting of the hAd5 vector appears to be more effective when the transduction mediated by retargeting ligands is directed through the .