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

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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.