Mammalian artificial chromosomes for gene transfer in livestock: Production of multi-transgenic pigs for xenotransplantation

用于家畜基因转移的哺乳动物人工染色体：用于异种移植的多转基因猪的生产

• 批准号: 118516965
• 负责人: Dr. Simone Kraner
• 金额: --
• 依托单位: Lehrstuhl für Biotechnologie der Nutztiere
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/118516965?language=en
• 关键词: Mammalian; artificial; chromosomes; gene; transfer

Xenotransplantation using tissues and organs from genetically modified pigs has the potential to fulfil the serious shortage of material available for human transplantation. However, considerable immunological barriers must be overcome before such discordant grafts can be used. The generation of α1-3 galactosyltransferase knock out pig lines has surmounted the initial obstacle of hyperacute rejection. Further improvements are now necessary to provide adequate protection against acute humoral xenograft rejection. The expression of human complement regulator transgenes in existing transgenic animals is inadequate, and a means of achieving abundant uniform expression in the organ is required. Recent findings have also highlighted the need for additional transgenes to alleviate incompatibilities between the porcine and human anticoagulation and antiinflammatory systems. We propose to address these problems using a novel approach. A de novo formed human artificial chromosome will be used as a vector to deliver sets of xenoprotective transgenes into pigs. The work will be carried out in close collaboration with the Xeno- Forschergruppe (FOR 535).

使用转基因猪的组织和器官进行异种移植，有可能解决人类移植材料严重短缺的问题。然而，在使用这种不协调的移植物之前，必须克服相当大的免疫障碍。α1-3半乳糖基转移酶基因敲除猪系的建立克服了超急性排斥反应的最初障碍。现在需要进一步的改进以提供足够的保护以对抗急性体液异种移植排斥。人补体调节剂转基因在现有转基因动物中的表达是不充分的，并且需要在器官中实现大量均匀表达的手段。最近的研究结果还强调了需要额外的转基因来缓解猪和人抗凝和抗凝系统之间的不相容性。我们建议使用一种新的方法来解决这些问题。从头形成的人类人工染色体将被用作载体，以将异种保护性转基因组递送到猪中。这项工作将与异种研究小组（FOR 535）密切合作进行。