PERV Free Swine for Xenotransplantation

描述（由申请人提供）：需要移植的患者数量与可用的器官捐献者数量之间存在巨大差距。猪可以很容易地解决未满足的需求。许多组织的生理机能与人类相近。它们可以在清洁可控的条件下饲养。然而，一个潜在的缺点是猪基因组中定义的一种病毒，PERV。在与人细胞系共培养的组织中，PERV可以传播到人细胞中。在人类或动物模型中尚未显示出任何感染或致病状态。PERV由三种病毒组成：PERV A、PERV B和PERV C。PERV A和PERV C是传播到人类细胞系的主要罪魁祸首。我们的项目为潜在的临床异种移植保留了一群非常干净的猪。用猪肝细胞进行的共培养试验未能将病毒传染给人类细胞。猪的PERV - C检测结果为阴性。多数为PERV - A阴性。一头猪对所有三种病毒以及PERV的通用gag/pol基因均呈阴性。这个应用程序将生成一群无PERV的猪。将用病毒学方法对这些猪进行PERV彻底评估。作为对可能的传染性的严格测试，人类细胞将在没有PERV的猪的子宫内培养。猪的器官移植对于解决人类器官供体严重短缺的问题可能是有价值的。有些器官，如心脏和胰岛，在生理上与人类非常相似。此外，猪可以在非常干净的控制条件下饲养。然而，人们对猪体内存在的一种病毒——猪内源性逆转录病毒（PERV）感到担忧。PERV是猪DNA的一部分，所以不能用传统方法根除。我们为临床异种移植维持的一群已经发现PERV非常少。一头猪似乎没有PERV病毒。这一应用将产生一个无PERV的猪群，用于临床异种移植。

DESCRIPTION (provided by applicant): There is a huge disparity between the number of patients who need a transplant and the available organ donors. Pigs could readily resolve the unmet need. The physiology of many tissues is close to that of humans. They can be raised in clean controlled conditions. One potential drawback, however, is a virus defined in the porcine genome, PERV. In tissue co-culture with human cell lines, PERV may be transmitted to the human cells. There has not yet been demonstrated any infectious or pathogenic state in humans or animal models. PERV consists of three viruses: PERV A, PERV B and PERV C. PERV A and PERV C are the primary culprits for transmission to human cell lines. Our program has maintained a herd of very clean pigs for potential clinical xenotransplantation. Co-culture tests with liver cells from our pigs failed to pass the virus to human cells. Screening the pigs, they are PERV C negative. The majority are PERV A negative. One pig is negative for all three viruses as well as the generic gag/pol gene for PERV. This application will generate a herd of PERV free pigs. These pigs will be thoroughly evaluated for PERV by virologic methods. As a stringent test for possible infectivity, human cells will be cultured in utero in PERV free pigs. PUBLIC HEALTH RELEVANCE Organ transplants from pigs could be valuable in resolving the severe shortage of human organ donors. Some organs, such as hearts and pancreatic islets, are physiologically very similar to humans. Furthermore, pigs can be raised under very clean controlled conditions. However, concern has been raised about a virus present in pigs, porcine endogenous retrovirus (PERV). PERV is part of the DNA of the pig, so it cannot be eradicated by conventional means. A herd that has been maintained by us for clinical xenotransplantation has been found to have very little PERV. One pig appears to be PERV free. This application would produce a PERV free swine herd for clinical xenotransplantation.