PERV Free Swine for Xenotransplantation

用于异种移植的无 PERV 猪

• 批准号: 7662508
• 负责人: WILLIAM Edward BESCHORNER
• 金额: $ 30万
• 依托单位: XIMEREX, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-22 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7662508
• 关键词: Animal Model; Archives; Biological Assay; Breeding; Cells; Clinical; Coculture Techniques; DNA; Endogenous Retroviruses; Environment; Family suidae; Gagging; Generations; Generic Drugs; Genome; Genomics; Goals; Grant; Guidelines; Health Hazards; Heart; Hepatocyte; Human; Human Cell Line; Immune Tolerance; Infection; Insulin-Dependent Diabetes Mellitus; Intention; Investigation; Islets of Langerhans; Kidney; Methods; Monitor; Nebraska; Organ; Organ Donor; Organ Transplantation; Parents; Pathology; Patients; Phase; Physiology; Probability; Proliferating; Public Health; Publishing; Regenerative Medicine; Research; Retroviridae Infections; Risk; Screening procedure; Siblings; Small Business Innovation Research Grant; Source; Testing; Tissues; Transplantation; Viral; Virion; Virus; Western Blotting; Xenograft procedure; end-stage organ failure; fetal; homologous recombination; in utero; islet; liver xenograft; offspring; pathogen; pol genes; pregnant; programs; public health relevance; tissue processing; transmission process

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.

描述(申请人提供)：需要移植的患者数量和现有的器官捐赠者之间存在着巨大的差距。猪可以很容易地解决未得到满足的需求。许多组织的生理学与人类相似。它们可以在干净受控的条件下饲养。然而，一个潜在的缺点是，猪基因组中定义了一种病毒PERV。在组织与人类细胞的共培养中，PERV可能被传染给人类细胞。目前还没有在人类或动物模型中证明有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。我们的项目保持了一群非常干净的猪，用于潜在的临床异种移植。与我们的猪的肝细胞共培养试验未能将病毒传递给人类细胞。对猪进行筛查，它们是PERV C阴性。大多数人是PERV A阴性。一头猪对这三种病毒以及PERV的普通Gag/Poll基因都是阴性的。这个应用程序将生成一群没有性变态的猪。这些猪将通过病毒学方法进行彻底的变态反应评估。作为对可能的传染性的严格测试，人类细胞将在无PERV的猪的子宫中培养。与公共卫生相关的猪器官移植在解决人类器官捐赠者严重短缺方面可能有价值。一些器官，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受控条件下饲养。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)--提出了担忧。PERV是猪DNA的一部分，因此无法通过常规方法根除。我们为临床异种移植维持的一个牛群被发现几乎没有性变态。有一头猪似乎没有性变态。这一应用将为临床异种移植培育一种无性变态反应的猪群。