Cotten M, Wagner E, Zatloukal K, Birnstiel M L
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
J Virol. 1993 Jul;67(7):3777-85. doi: 10.1128/JVI.67.7.3777-3785.1993.
Delivery of genes via receptor-mediated endocytosis is severely limited by the poor exit of endocytosed DNA from the endosome. A large enhancement in delivery efficiency has been obtained by including human adenovirus particles in the delivery system. This enhancement is probably a function of the natural adenovirus entry mechanism, which must include passage through or disruption of the endosomal membrane. In an effort to identify safer virus particles useful in this application, we have tested the chicken adenovirus CELO virus for its ability to augment receptor-mediated gene delivery. We report here that CELO virus possesses pH-dependent, liposome disruption activity similar to that of human adenovirus type 5. Furthermore, the chicken adenovirus can be used to augment receptor-mediated gene delivery to levels comparable to those found for the human adenovirus when it is physically linked to polylysine ligand-condensed DNA particles. The chicken adenovirus has the advantage of being produced inexpensively in embryonated eggs, and the virus is naturally replication defective in mammalian cells, even in the presence of wild-type human adenovirus.
通过受体介导的内吞作用进行基因传递受到内吞的DNA难以从内涵体中逸出的严重限制。通过在传递系统中加入人腺病毒颗粒,传递效率得到了大幅提高。这种提高可能是天然腺病毒进入机制的作用,该机制必然包括穿过或破坏内涵体膜。为了确定在该应用中有用的更安全的病毒颗粒,我们测试了鸡腺病毒CELO病毒增强受体介导的基因传递的能力。我们在此报告,CELO病毒具有与5型人腺病毒类似的pH依赖性脂质体破坏活性。此外,当鸡腺病毒与聚赖氨酸配体凝聚的DNA颗粒物理连接时,它可用于将受体介导的基因传递提高到与人腺病毒相当的水平。鸡腺病毒具有在鸡胚中廉价生产的优势,并且该病毒在哺乳动物细胞中天然存在复制缺陷,即使存在野生型人腺病毒也是如此。