Proteogenomics Research Institute for Systems Medicine, 11107 Roselle St., San Diego, CA 92121, USA.
Virol J. 2010 Nov 12;7:316. doi: 10.1186/1743-422X-7-316.
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 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.
基于腺病毒的基因传递载体，特别是人类腺病毒血清型 5（hAd5），具有治疗多种疾病的巨大潜力。然而，为了使该载体系统成功应用于临床，需要对 hAd5 的亲嗜性进行修饰，以实现组织或细胞特异性治疗。在这里，我们通过用生物素接受肽（Propionibacterium shermanii 1.3 S 转羧酶结构域（PSTCD）的截断形式）替换包含柯萨奇病毒 B 和腺病毒受体（CAR）结合位点的纤维旋钮，修饰了 hAd5 的亲嗜性，从而使病毒能够进行代谢生物素化。我们在这里证明，新型腺病毒不再表现出依赖 CAR 的细胞摄取和转导。当被代谢生物素化并用亲和素包被时，它形成一个纳米复合物，可以使用生物素化抗体将其重新靶向到不同的细胞。该载体可能在实现靶向基因传递的道路上证明是有用的。
