Department of Chemistry, State University of New York at Stony Brook , Stony Brook, NY 11794-3400, USA.
Bioconjug Chem. 2012 Jul 18;23(7):1370-6. doi: 10.1021/bc200477z. Epub 2012 Jun 22.
Methods for targeting oncolytic viruses can increase efficacy and accelerate development. Genetic engineering, the predominant method for changing vector tropism, is limited in scope and often represents the bottleneck for vector development. Metabolic incorporation of an unnatural azido sugar, O-GlcNAz, at a specific site on the adenoviral surface allows chemoselective attachment of affibodies for Her2 or EGF receptors. Modification with these high-affinity, high-selectivity proteins is straightforward and readily generalizable, demonstrates minimal impact on virus physiology, and affords significant increases in gene delivery to cancer cells. As a result, this method has significant potential to increase the efficacy of next-generation viral vectors.
肿瘤溶瘤病毒的靶向方法可以提高疗效并加速开发。遗传工程是改变载体趋向性的主要方法，但范围有限，通常代表载体开发的瓶颈。在腺病毒表面的特定位置上将非天然的叠氮糖 O-GlcNAz 掺入代谢物中，允许阿非布地对 Her2 或 EGF 受体进行化学选择性附着。用这些高亲和力、高选择性的蛋白质进行修饰既简单又易于推广，对病毒生理学的影响很小，并显著增加了向癌细胞的基因传递。因此，这种方法具有显著提高下一代病毒载体疗效的潜力。
