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

在传统的原核生物和真核生物培养系统中表达哺乳动物蛋白有许多不足之处。这些缺点可能会妨碍它们在生物反应器中成功地用于大规模生产翻译后修饰蛋白。值得注意的是，大多数人类蛋白质具有显著程度的翻译后修饰。即使哺乳动物组织培养系统拥有必要的酶机制来进行这些修饰，在固有的培养不稳定性和表达水平方面也有局限性。组织培养所需培养基的高成本使问题更加复杂。初步研究表明，这些问题都可以通过在大型动物中进行转基因表达来克服。有必要对基础转基因生物学的当前发展进行评估，以使其潜力得到关注和推进，成为当前新兴生物技术领域的一部分。这是研讨会的主要目标，题为“弗吉尼亚湖大型转基因动物生物反应器研讨会前和小型研讨会”。大规模生产具有治疗价值的蛋白质现在只针对极少数蛋白质进行。这些蛋白质要么像胰岛素一样是非常简单的分子，要么在一次性灾难性事件中少量有效。这就是组织纤溶酶原激活剂（TPA）的情况，TPA是一种用于治疗正在进行中的心脏病发作的蛋白质。TPA是一个说明性的例子，因为它的成本和有限的可用性是如此令人难以接受，以至于将其限制在（几乎完全）急诊室的情况下使用。蛋白质只能作为慢性治疗（因此，在长期基础上）有效，通常没有足够的数量或生物活性形式，如目前的生物反应器技术生产。利用转基因奶牛作为生物反应器，通过其在牛奶中制造蛋白质的无与伦比的能力，可能为这些蛋白质生产僵局提供解决方案。保守估计，一头普通（转基因）奶牛每年生产的任何一种重要的治疗性蛋白质都超过数千万美元。这种农业和生物技术的结合必然会为乳制品和养牛业以及目前因无法获得治疗性蛋白质而死亡的人们带来新的生命。

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.