NONHUMAN ADENOVIRUS VECTORS FOR GENE THERAPY

描述：设计一辆合适的送货工具对 在基因治疗方案中获得所需的结果。人腺病毒 最近吸引了相当大的兴趣，因为它们可能被用作 基因治疗的输送载体，特别是用于基因治疗的载体 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了一些病毒基因，因此， 携带所需载体的细胞从循环中移除，从而 在短时间内进行转基因表达。这表明有一个 需要进一步削弱病毒以获得转基因表达 延长了一段时间。非人腺病毒，如牛腺病毒 不复制的3型(BAd3)和猪腺病毒3型(PAD3) 但可以在培养中感染人类细胞，可以提供一种 诱人的替代人腺病毒载体用于基因治疗。 长期目标是培育复制缺陷的BAd3和PAD3 用于人类基因治疗的载体，目的是获得 所需基因长时间无明显副作用。 最初，这些含有报告基因的载体将在人类身上进行测试 以评估细胞系和实验动物的水平和持续时间 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，炎症性 动物接种部位的反应和宿主的免疫反应 对向量的攻击。这些实验将为未来奠定基础 研究最初是在人体组织中进行的，随后进行了一项小型人体试验 使用BAd3或PAD3载体纠正呼吸道、肝脏或 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.