Seth P
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Biochem Biophys Res Commun. 1994 Aug 30;203(1):582-7. doi: 10.1006/bbrc.1994.2222.
Human adenovirus type 2 has been previously shown to increase the delivery of a variety of proteins into cells when Ad is co-internalized with the protein ligands. To increase the efficiency of adenoviral-mediated delivery of proteins, I have linked adenovirus, separately with two proteins, epidermal growth factor and an antibody against human transferrin receptor through disulfide and thioether linkages. Competition experiments indicate that the conjugates are taken up into the cells through adenovirus receptor. During the internalization of adenovirus-protein conjugates into KB cells, the conjugates were equally effective as the native adenovirus in disrupting endocytic vesicles and releasing their protein content into the cytosol. This implies the possible use of adenovirus to deliver a large number of protein molecules into the cells.
先前的研究表明，当腺病毒（Ad）与蛋白质配体共同内化时，2型人腺病毒可增加多种蛋白质向细胞内的递送。为提高腺病毒介导的蛋白质递送效率，我通过二硫键和硫醚键将腺病毒分别与两种蛋白质——表皮生长因子和抗人转铁蛋白受体抗体连接起来。竞争实验表明，这些偶联物通过腺病毒受体被细胞摄取。在腺病毒-蛋白质偶联物内化进入KB细胞的过程中，这些偶联物在破坏内吞小泡并将其蛋白质内容物释放到细胞质中方面与天然腺病毒同样有效。这意味着腺病毒有可能用于将大量蛋白质分子递送至细胞内。
