Preworkshop and Mini-Symposium for the Assessment of Transgenic Large Animals as Bioreactors to be held in Mountain Lake, Virginia, November 16-18, 1988

转基因大型动物生物反应器评估预研讨班和小型研讨会将于 1988 年 11 月 16 日至 18 日在弗吉尼亚州山湖举行

• 批准号: 8822916
• 负责人: William Velander
• 金额: $ 0.75万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-11-15 至 1989-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8822916&HistoricalAwards=false
• 关键词: Preworkshop; Mini; Symposium; Assessment; Transgenic

The expression of mammalian proteins in conventional procaryotic and eukaryotic culture systems has many inadequacies. These shortcomings may preclude their successful utilization in bioreactors for the large-scale production of post-translational modified proteins. It is important to note that most human proteins possess a significant degree of post-translational modification. Even mammalian tissue culture systems which possess the necessary enzymatic machinery to make these modifications have limitations both with respect to inherent culture instability and expression levels. This is complicated by the high cost of culture media required for tissue culture. Preliminary research indicates that all of the above problems may be overcome by transgenic expression in large animals. An assessment of the current developments in basic transgenic biology is necessary such that its potential can be focused and advanced to become a part of the current gamut of emerging biotechnologies. This is a main goal of the workshop entitled, "Mt. Lake Va. Preworkshop and Minisymposium on Large Transgenic Animals as Bioreactors." The large-scale production of proteins which have therapeutic value is now performed for only a very few proteins. These proteins are either very simple molecules such as insulin or are effective in small quantities for one-time catastrophic events. This is the case for tissue plasminogen activator (TPA) which is a protein used in the treatment of a heart attack which is in progress. TPA is an illustrative example as its cost and limited availability are so prohibitive as to confine its use to (almost exclusively) emergency room situations| Proteins which are only effective as chronic therapies (ergo, on a long term basis) are not as a rule available in sufficient quantity or in a biologically active form as produced by current bioreactor technology. The use of transgenic cows as bioreactors may provide the solution to these protein production impasses through its unsurpassed ability to make protein in milk. Conservative estimates have put a single, average (transgenic) cow's annual production of any given important therapeutic protein in excess of tens of millions of dollars. This agricultural- biotechnological marriage would necessarily breathe new life into both the dairy and cattle industries as well as the people who now die as result of the unavailability of therapeutic proteins.

哺乳动物蛋白质在常规原核和 真核培养系统有许多不足之处。 这些缺点 可能妨碍它们在生物反应器中的成功利用， 翻译后修饰蛋白的大规模生产。 是 值得注意的是，大多数人类蛋白质具有显著的 翻译后修饰的程度。 甚至哺乳动物组织 培养系统具有必要的酶机制， 使这些修改具有限制， 固有的培养不稳定性和表达水平。 这是 由于组织培养所需的培养基成本高， 文化 初步研究表明，上述所有 通过在大型动物中进行转基因表达可以克服这些问题。 对基础转基因生物学发展现状的评价 是必要的，以便其潜力可以集中和推进， 成为当前新兴生物技术领域的一部分。 这 这是一个主要目标的讲习班，题为“山。弗吉尼亚湖研讨会前和 大型转基因动物作为生物反应器的最小对称性。" 具有治疗价值的蛋白质的大规模生产是 现在只对极少数蛋白质进行了测试。 这些蛋白质要么是 非常简单的分子，如胰岛素，或者在小分子中有效， 一次性灾难性事件的数量。 就是这种情况 组织纤溶酶原激活物（TPA）， 一种用于治疗心脏病发作的蛋白质， 中求进工作总 TPA是一个说明性的例子，因为它的成本和限制 可用性是如此令人望而却步，以限制其使用（几乎 急诊室情况|这些蛋白质只 有效的慢性疗法（因此，在长期的基础上）， 通常没有足够的数量或 由现有生物反应器生产的生物活性形式 技术. 使用转基因奶牛作为生物反应器， 为这些蛋白质生产的僵局提供解决方案， 它在牛奶中制造蛋白质的能力无与伦比。 保守 据估计，一头平均（转基因）奶牛每年 过量生产任何给定的重要治疗性蛋白质 价值数千万美元。 这个农业- 生物技术婚姻必然会给人类带来新的生命， 奶制品和养牛业以及那些 现在由于治疗性蛋白质的不可用而死亡。