O'Riordan Catherine R, Song Antonius
Genzyme Corporation, Framingham, MA, USA.
Methods Mol Biol. 2008;434:133-60. doi: 10.1007/978-1-60327-248-3_9.
Bifunctional polyethylene glycol (PEG) molecules provide a novel approach to retargeting viral vectors without the need to genetically modify the vector. Modification of the surface of adenovirus with heterofunctional PEG allows further modification of the capsid with ligands. In addition, heterofunctional PEG modification ablates the normal tropism of the virus and reduces transduction of non-target tissues in vivo. Moreover, the addition of PEG chains to the surface of the virus shields antigen-binding sites, significantly reducing the susceptibility of the virus to antibody neutralization. Finally, T cell subsets from mice exposed to the PEGylated vector demonstrate a marked decrease in Th1 and Th2 responses, suggesting that PEG modification may help reduce the immune response to the vector.
双功能聚乙二醇（PEG）分子提供了一种无需对载体进行基因改造即可重新靶向病毒载体的新方法。用异功能PEG修饰腺病毒表面，可进一步用配体修饰衣壳。此外，异功能PEG修饰消除了病毒的正常嗜性，并减少了体内非靶组织的转导。而且，在病毒表面添加PEG链可屏蔽抗原结合位点，显著降低病毒对抗体中和的敏感性。最后，暴露于聚乙二醇化载体的小鼠的T细胞亚群显示Th1和Th2反应明显降低，这表明PEG修饰可能有助于降低对载体的免疫反应。
