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转基因生物反应器

Transgenic bioreactors.

作者信息

Jänne J, Hyttinen J M, Peura T, Tolvanen M, Alhonen L, Sinervirta R, Halmekytö M

机构信息

Department of Biochemistry & Biotechnology, University of Kuopio, Finland.

出版信息

Int J Biochem. 1994 Jul;26(7):859-70. doi: 10.1016/0020-711x(94)90078-7.

DOI:10.1016/0020-711x(94)90078-7
PMID:8063010
Abstract
  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. 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. 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 in the milk. 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.
摘要
  1. 尽管目前许多人类治疗性蛋白质是利用重组DNA技术在微生物发酵罐中生产的,但由于细菌无法进行实现完全生物活性所需的合成后修饰反应,显然微生物加工不适用于大量生物活性蛋白质。2. 这一缺点不适用于能够产生具有完全生物活性实体的动物细胞生物反应器,但将大规模动物细胞培养用于生产目的成本高得令人望而却步。3. 随着转基因技术的出现,在大型农场动物(猪、绵羊、山羊和奶牛)中生产有价值的人类药物作为一种高产量、低成本的替代方案变得越来越有吸引力。通过采用靶向基因转移,例如使用与所需生产基因融合的乳腺特异性调控序列,有可能使表达仅在乳腺中发生,因此基因产物最终会分泌到乳汁中。4. 在回顾该领域取得的显著进展甚至已导致商业开发的同时,我们将更详细地概述我们利用奶牛作为生物反应器生产具有药用价值蛋白质的策略。

相似文献

1
Transgenic bioreactors.转基因生物反应器
Int J Biochem. 1994 Jul;26(7):859-70. doi: 10.1016/0020-711x(94)90078-7.
2
Transgenic animals as bioproducers of therapeutic proteins.作为治疗性蛋白质生物生产器的转基因动物。
Ann Med. 1992 Aug;24(4):273-80. doi: 10.3109/07853899209149954.
3
Transgenic bioreactors.转基因生物反应器
Biotechnol Annu Rev. 1998;4:55-74. doi: 10.1016/s1387-2656(08)70067-x.
4
Developing efficient strategies for the generation of transgenic cattle which produce biopharmaceuticals in milk.开发高效策略以培育能在乳汁中产生生物制药产品的转基因牛。
Theriogenology. 2000 Jan 1;53(1):139-48. doi: 10.1016/s0093-691x(99)00247-2.
5
Producing recombinant human milk proteins in the milk of livestock species.在牲畜的乳汁中生产重组人乳蛋白。
Adv Exp Med Biol. 2008;606:357-93. doi: 10.1007/978-0-387-74087-4_15.
6
The mammary gland as a bioreactor: expression, processing, and production of recombinant proteins.作为生物反应器的乳腺:重组蛋白的表达、加工与生产
J Mammary Gland Biol Neoplasia. 1998 Jul;3(3):337-50. doi: 10.1023/a:1018723712996.
7
Transgenic animal bioreactors.转基因动物生物反应器
Transgenic Res. 2000;9(4-5):305-20. doi: 10.1023/a:1008934912555.
8
Genetically modified livestock for the production of human proteins in milk.用于在牛奶中生产人类蛋白质的转基因家畜。
Biotechnol Genet Eng Rev. 1998;15:33-49. doi: 10.1080/02648725.1998.10647951.
9
[Production of pharmaceutical proteins with mammary gland bioreactor].利用乳腺生物反应器生产药用蛋白质
Sheng Wu Gong Cheng Xue Bao. 2000 Jul;16(4):421-4.
10
Transgenic dairy cattle: genetic engineering on a large scale.转基因奶牛:大规模基因工程
J Dairy Sci. 1997 Sep;80(9):2213-24. doi: 10.3168/jds.S0022-0302(97)76170-8.

引用本文的文献

1
Establishment of mammary gland model in vitro: culture and evaluation of a yak mammary epithelial cell line.体外乳腺模型的建立:牦牛乳腺上皮细胞系的培养与鉴定
PLoS One. 2014 Dec 5;9(12):e113669. doi: 10.1371/journal.pone.0113669. eCollection 2014.
2
Renal tubule-specific expression and urinary secretion of human growth hormone: a kidney-based transgenic bioreactor growth.人生长激素的肾小管特异性表达及尿液分泌:基于肾脏的转基因生物反应器生长
Transgenic Res. 2003 Apr;12(2):155-62. doi: 10.1023/a:1022967505222.
3
Production of transgenic miniature pigs by pronuclear microinjection.
通过原核显微注射生产转基因小型猪。
Transgenic Res. 2001 Dec;10(6):577-82. doi: 10.1023/a:1013059917280.