Department of Biological Sciences and Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
J Control Release. 2010 Mar 3;142(2):238-44. doi: 10.1016/j.jconrel.2009.11.001. Epub 2009 Nov 12.
Polyethylene glycol (PEG) has been chemically immobilized onto the surface of adenoviruses (ADVs) to reduce non-specific immune response and extend blood circulation time while maintaining the high transduction efficiency of a foreign gene into cells. In this study, ADVs encoding an exogenous green fluorescent protein (GFP) were physically coated with PEG grafted and blocked poly-L-lysine (PLL-g-PEG and PLL-b-PEG) copolymers via ionic interactions to comparatively evaluate their gene transduction efficiency. The surface immobilization of ADVs with the two types of PLL-PEG copolymers exhibited significantly increased GFP transduction activity, compared to that of naked ADVs. ADVs coated with PLL-b-PEG showed higher extent of GFP expression than those with PLL-g-PEG under serum conditions. For PLL-g-PEG copolymers, the substitution degree of PEG in the PLL backbone greatly influenced the gene expression level. Additionally, ADVs modified with PLL-b-PEG exhibited greater transduction efficiency for bone marrow derived human mesenchymal stem cells compared to naked or PLL coated ADVs in the serum condition. This study suggests that enhanced ADV gene transduction efficiency can be attained for various cells by simply coating PLL-b-PEG on the surface.
聚乙二醇（PEG）已通过化学方法固定在腺病毒（ADV）表面，以减少非特异性免疫反应并延长血液循环时间，同时保持将外源基因高效转染入细胞的能力。在本研究中，通过离子相互作用将物理包被有聚乙二醇接枝和封端聚-L-赖氨酸（PLL-g-PEG 和 PLL-b-PEG）共聚物的 ADV 编码外源绿色荧光蛋白（GFP），以比较评估其基因转导效率。与裸 ADV 相比，两种类型的 PLL-PEG 共聚物表面固定的 ADV 显示出 GFP 转导活性明显增加。在血清条件下，与 PLL-g-PEG 包被的 ADV 相比，PLL-b-PEG 包被的 ADV 显示出更高的 GFP 表达水平。对于 PLL-g-PEG 共聚物，PLL 主链中的 PEG 取代度极大地影响基因表达水平。此外，与裸 ADV 或 PLL 包被的 ADV 相比，PLL-b-PEG 修饰的 ADV 在血清条件下对骨髓来源的人间充质干细胞具有更高的转导效率。本研究表明，通过简单地将 PLL-b-PEG 涂覆在 ADV 表面上，可以提高各种细胞的 ADV 基因转导效率。
