Production of genetically modified chickens resistant to important avian respiratory diseases.

我们的最终目标是提高家畜对病毒性疾病的抵抗力。这对动物健康和福利具有重要意义，但鸟类和猪也可以作为桥接宿主，使新型流感病毒株能够引起人类感染。目前，我们把重点放在鸡身上，作为确定实现这一目标的最有效方法的试验台。生产抗禽流感的鸡将减少在人类中出现新的大流行性流感病毒的威胁，有助于全球粮食安全，并减少控制家禽感染的经济后果。我们的方法是将新的基因引入到鸡的基因组中，这些基因被流感感染激活，并产生特异性和有效抑制病毒复制的分子。这些分子本质上对鸡无害，食用是安全的，在没有病毒感染的情况下，其产量非常低。流感病毒感染导致这些抑制分子的产生增加，这些抑制分子要么直接干扰病毒复制机制，要么触发具有抗病毒特性的正常细胞蛋白的产生。该项目包括首先在细胞培养中构建和测试一系列不同的抑制基因，然后使用基因改造技术将最有效的基因引入鸡体内。然后对这些转基因鸟类进行测试，以确定它们是否对AI感染具有抵抗力。该项目被描述为管道，因为各种抑制性转基因已经达到了不同的发展阶段。有些已经在转基因鸡身上被证明是有效的，有些在细胞培养中，还有一些仍处于概念阶段。大部分的研究都是针对流感病毒的。然而，一些初步的工作被提出，以确定是否可以开发类似的方法来对付其他重要的禽流感病毒感染。

Our ultimate objective is to improve the resistance of livestock species to viral diseases. . This has important implications for animal health and welfare but avian species and pigs can also act as bridging hosts that enable novel strains of influenza virus to cause infection in humans. Currently we are focusing on chickens as a test-bed for identifying the most effective ways to achieve this objective. Producing AI resistant chickens would reduce the threat of a new pandemic influenza virus emerging in humans, contribute to global food security and decrease the economic consequences of controlling the infection in poultry. Our approach is to introduce novel genes into the chicken genome that become activated by influenza infection and produce molecules that specifically and potently suppress virus replication. These molecules are intrinsically harmless to the chicken, safe for consumption and in the absence of virus infection are produced at very low levels. Influenza virus infection results in the increased production of these inhibitory molecules which then either interfere directly with the virus replication machinery or trigger the production of normal cellular proteins with antiviral properties.The project involves the construction and testing of a series of different inhibitory genes firstly in cell culture and then introducing the most effective ones into chickens using genetic modification techniques. These transgenic birds are then tested to determine whether they are resistant to AI infection. The project is described as a pipeline because the various inhibitory transgenes have reached different stages of development. Some have already been shown to be effective in GM chickens, some in cell culture and others are still at the conceptual phase. Most of the work is aimed at influenza virus. However, some preliminary work is proposed to determine whether similar approaches can be developed against other important avian virus infections.