Construction of Metabolically Biotinylated Adenovirus with Deleted Fiber Knob as Targeting Vector

• Main Authors: Schnitzer Jan E, Valadon Philippe, Liu Yanzheng
• Format: Article
• Language: English
• Published: BMC 2010-11-01
• Series: Virology Journal
• Online Access: http://www.virologyj.com/content/7/1/316

<p>Abstract</p> <p>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 <it>Propionibacterium shermanii </it>1.3 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 nano-complex that can be retargeted to distinct cells using biotinylated antibodies. This vector may prove useful in the path towards achieving targeted gene delivery.</p>