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（由申请人提供）：需要移植的患者数量与可用器官捐赠者的患者数量存在很大差异。猪可以很容易地解决未满足的需求。许多组织的生理与人类的生理相关。它们可以在干净的受控条件下提高。然而，一个潜在的缺点是在猪基因组中定义的病毒。在与人类细胞系共培养的组织共培养中，可能会传播到人类细胞。在人类或动物模型中，尚未证明任何传染性或致病状态。 PERV由三种病毒组成：PERV A，PERV B和PERV C. PERV A和PERV C是向人类细胞系传播的主要罪魁祸首。我们的计划维持了一群非常干净的猪，以进行潜在的临床异种移植。与我们猪的肝细胞共培养测试未能将病毒传递给人类细胞。筛选猪，它们呈阴性。大多数都是负面的。一只猪对所有三种病毒以及PERV的通用插孔/POL基因均为阴性。该应用程序将产生一群无毛病的猪。这些猪将通过病毒学方法对PERV进行彻底评估。作为对可能感染性的严格测试，人类细胞将在无用的猪中在子宫内培养。公共卫生相关性的器官移植物可能在解决严重的人体器官捐献者的严重短缺方面很有价值。某些器官，例如心脏和胰岛，在生理上与人类非常相似。此外，可以在非常干净的控制条件下饲养猪。然而，人们对猪内源性逆转录病毒（PERV）中存在的病毒提出了关注。 PERV是猪的DNA的一部分，因此无法通过常规手段消除它。我们已经发现，我们已经为临床异种移植而维持的一群人几乎没有perv。一只猪似乎无所不能。该应用将产生一个无处不在的猪群，用于临床异种移植。