转基因生物反应器

Juhani Jänne, Juha-Matti Hyttinen, Teija Peura, Minna Tolvanen, Leena Alhonen, Rlitta Sinervirta, Maria Halmekytö
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引用次数: 6

摘要

1.1. 尽管目前许多人类治疗性蛋白是利用重组DNA技术在微生物发酵罐中生产的,但很明显,由于细菌无法进行完全生物活性所需的合成后修饰反应,微生物加工不适合大量生物活性蛋白。这一缺点并不适用于能够产生生物完全活性实体的动物细胞生物反应器,然而,用于生产目的的大规模动物细胞培养物的使用过于昂贵。随着转基因技术的出现,利用大型农场动物(猪、绵羊、山羊和奶牛)生产有价值的人类药物作为一种高质量、低成本的替代方法越来越有吸引力。通过使用靶向基因转移,例如使用乳腺特异性调控序列与所需的生产基因融合,可以控制表达仅发生在乳腺中,因此基因产物最终被分泌到乳汁中。在回顾这一领域的显著进展,甚至导致商业开发的同时,我们将更详细地概述我们的战略,即利用奶牛作为有价值的药物蛋白质的生物反应器。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transgenic bioreactors

  • 1.

    1. Although many human therapeutic proteins are currently produced in microbial fermentors using recombinant DNA techniques, it is obvious that microbial processing is not suitable for a large number of bioactive proteins owing to the inability of bacteria to carry out postsynthetic modification reactions required for full biological activity.

  • 2.

    2. This disadvantage does not apply to animal cell bioreactors that can generate biologically fully active entities, yet the use of large-scale animal cell cultures for production purposes is prohibitively expensive.

  • 3.

    3. With the advent of transgenic technology, the production of valuable human pharmaceuticals in large farm animals (pig, sheep, goat and dairy cattle) has become more and more attractive as a high-quantity, low-cost alternative. By employing targeted gene transfer, e.g. using mammary gland-specific regulatory sequences fused with the desired production genes, it is possible to govern the expression to occur exclusively in the mammary gland and hence the gene product is being ultimately secreted into the milk.

  • 4.

    4. While reviewing the remarkable progress in this field that has even led to commercial exploitations, we will outline in somewhat greater detail our strategy for the use of dairy cattle as a bioreactor for valuable proteins of pharmaceutical interest.

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