NONHUMAN ADENOVIRUS VECTORS FOR GENE THERAPY

描述：设计合适的运载工具非常重要， 在基因治疗方案中获得期望的结果。 人腺病毒 最近吸引了相当大的兴趣，因为它们可能用作 用于基因治疗特别是用于治疗遗传病的递送载体 疾病和癌症。 现在已经充分认识到，目前 可用的载体确实表达一些病毒基因，因此， 将携带所需载体的细胞从循环中除去， 在转基因表达中持续很短时间。 这表明， 需要进一步削弱病毒才能获得转基因表达， 延长时间。 非人腺病毒，如牛腺病毒 3型（BAd3）和猪腺病毒3型（PAd3），它们在 人类细胞，但可以感染培养中的人类细胞，可以提供一种 用于基因治疗的人腺病毒载体的有吸引力的替代物。 长期目标是开发复制缺陷型BAd3和PAd3， 用于人类基因治疗的载体，目的是获得 在没有明显副作用的情况下， 最初，这些含有报告基因的载体将在人类中进行测试。 细胞系和实验动物，以评估 转基因表达，载体的早期和晚期基因表达水平， 载体DNA存在的状态和持续时间，炎症反应， 动物接种部位的免疫应答和宿主免疫应答 与矢量进行对比。 这些实验将成为未来的基础 最初在人体组织中进行研究，随后在小型人体试验中进行研究 使用BAd3或PAd3载体校正呼吸、肝或 心血管疾病或癌症治疗。

DESCRIPTION: Designing a suitable delivery vehicle is very important to obtain the desired results in a gene therapy protocol. Human adenoviruses have attracted considerable interest lately for their potential use as delivery vehicles for gene therapy especially for treating genetic disorders, and cancer. Now it has been fully realized that currently available vectors do express some of the viral genes, and therefore, the cells carrying the desired vector are removed from the circulation resulting in transgene expression for a short duration. This suggests that there is a need to cripple the virus further to obtain transgene expression for an extended period of time. Non-human adenoviruses, such as bovine adenovirus type 3 (BAd3) and porcine adenovirus type 3 (PAd3) that do not replicate in human cells but can infect human cells in culture, could provide an attractive alternative to human adenovirus vectors for gene therapy. The long-term objectives are to develop replication-deficient BAd3 and PAd3 vectors for human gene therapy with a purpose of obtaining expression of the desired gene for a long period of time without significant side effects. Initially these vectors containing a reporter gene will be tested in human cell lines and experimental animals to evaluate the level and duration of transgene expression, the levels of vector's early and late gene expression, the state and duration of the presence of vector DNA, the inflammatory response at the site of inoculation in animals, and the host immune response against the vector. These experiments will form the basis for the future studies initially in human tissues and subsequently in a small human trial using either BAd3 or PAd3 vector for correcting a respiratory, hepatic or cardiovascular disorder or in cancer therapy.