The Establishment of Gene Therapy with and Gene Expression Regulation of Adenoviral Vector Serotype 35

腺病毒载体（Ad）具有一些吸引人的特性，包括高转导效率、广泛的分裂和非分裂细胞转导以及不随机整合到宿主基因组中。2005年和2006年成功地进行了两项使用腺病毒载体的I期临床试验，一项是在儿科人群中，另一项是在老年人人群中。然而，由于Ad血清型5在人群中高度流行，许多个体暴露于Ad5并随后产生剂量依赖性中和抗体反应。许多人认为，这种针对ad5的抗体反应有助于缩短转基因表达的持续时间，这被认为是腺病毒载体治疗的一个缺点。在这项研究中，我们提供的证据表明，与传统的Ad5相比，视网膜下递送的Ad35和Ad28基因表达时间更长。这些事实为开发适用于诸如年龄相关性黄斑变性等眼部疾病的发病机制和治疗的治疗性蛋白制剂奠定了基础。

Adenoviral vectors(Ad) have several attractive properties, including high transduction efficiency, transduction of a wide spectrum of dividing and non-dividing cells and absence of random integration into the host genome. Two phase I clinical trials using adenoviral vector have successfully been conducted in 2005 and 2006, one in a pediatric population, and the other in an elderly population. However, since Ad serotype 5 is highly prevalent in the human population, many individuals have been exposed to Ad5 and subsequently, have generated a dose-dependent neutralizing antibody response. This antibody response toAd5 is thought by many to contribute to a shorter duration of transgene expression, which is considered to be a disadvantage of adenoviral vector therapy. In this study we provided the evidence that Ad35 and Ad28 delivered subretinally gave prolonged gene expression as compared to conventional Ad5. These facts indicate the basis for the development of therapeutic protein agents that are applicable to the pathogenesis and treatment of ocular diseases such as age-related macular degeneration.