• 한국생물공학회:학술대회논문집
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• 2002.04a
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• pp.269-270
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• 2002

Oxygen is a key substrate in animal cell metabolism and its consumption is thus a parameter of great interest for monitoring and control in animal cell culture bioreactor. The use of a gas-permeable membrane offered the possibility to provide the required quantity of oxygen into the culture. while avoiding problems of foaming or shear damage generally linked to sparging. For determining the optimum DO control strategy of this gas-permeable membrane aeration bioreactor, the oxygen transfer rate coefficient was measured with varying $N_2$ ratio in inlet air. The results showed that an increasing mass flow rate of nitrogen reduced the $K_La$ value. and 5% nitrogen in air did not result in any oxygen limitation.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 1998.07a
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• pp.8-11
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• 1998

• 대한생식의학회:학술대회논문집
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• 2001.03a
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• pp.217-219
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• 2001

• KSBB Journal
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• v.6 no.3
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• pp.231-240
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• 1991

Recently, developments of large scale and high density cell culture methods have been the objects of many researches, because the demand of various pharmaceutical products produced by animal cell culture has been rapidly increasing. The cell culture equipment should have the requirements such as sufficient oxygen transfer and mixing, low shear stress and surface tension, and small foaming. In order to develop a proper bioreactor meeting these requirements simultaneously, a perfluorocarbon having high solubility of oxygen was sprayed into the medium as an oxygen carrier instead of air. Also, a new impeller was developed and combined together with the perfluorocarbon spraying system so as to design a new bioreartor for cell cultivation. The new impeller had better characteristics of mixing and oxygen transfer than the paddle and cell-lift impellers based on the same, shear rate. But, it was observed that the volumetric oxygen transfer coefficient of the new bioreactor decreased with increasing cell density during E. coli fermentation.

• Applied Chemistry for Engineering
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• v.5 no.6
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• pp.911-916
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• 1994

Hollow fiber membrane has been successfully developed as an artificial kidney device in the 1970's. In the early 1970's animal cells were introduced into a hollow fiber membrane cartridge and well propagated in the cartridge. Since then, hollow fiber membrane was utilized as a bioreactor in order to immobilize enzymes as well as to culture microbial cells and plant cells. In this review, the present status and the prospect of hollow fiber membrane bioreactor are investigated in view of cell density and product productivity.

• Microbiology and Biotechnology Letters
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• v.21 no.4
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• pp.348-353
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• 1993

The optimal conditions for operating a moving-aeration bioreactor were determined as 30rpm and 150 (ml/min) of air flow rate, which can yield ca. 7.3 (l/h)of maximum mass transfer coefficient. It was also found that the agitation speed played much much important role than air input rate in oxgen transfer into the medium. $2.6{\times}10^6$ (cells/ml) and 0.6 (ml/l) of maximum cell denisty and IL-2 production were observed in batch cultivation of IL-2 producing BHK cell line. 0.53 (mM/l/h) of oxygen uptake rate was also estimated. The performance of a moving-aeration bioreactor (specific growth rate and oxygen uptake rate, etc.) was superior to other culture systems, such as cell-life and static membrane aeration bioreactors. Ii must be useful to apply this reactor to many culture processes by improving structural limitations in scaling-up the system.

• Journal of Microbiology and Biotechnology
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• v.19 no.12
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• pp.1695-1702
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• 2009

An animal-component-free and chemically defined fed-batch process for GS-engineered cell lines producing recombinant antibodies has been developed. The fed-batch process relied on supplying sufficient nutrients to match their consumption, simultaneously minimizing the accumulation of by-products (lactate and osmolality). The proportionalities of nutritional consumption were determined by direct analysis. The robust, metabolically responsive feeding strategy was based on the offline measurement of glucose. The fed-batch process was shown to perform equivalently in GS-CHO and GS-NS0 cultures. Compared with batch cultures, the fed-batch technology generated the greater increase in cell yields (5-fold) and final antibody concentrations (4-8-fold). The majority of the increase in final antibody concentration was a function of the increased cell density and the prolonged culture time. This generic and high-yielding fed-batch process would shorten development time, and ensure process stability, thereby facilitating the manufacture of therapeutic antibodies by GS-engineered cell lines.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.6
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• pp.806-813
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• 2010

Animal bioreactors have been regarded as alternative tools for the production of limited human therapeutic proteins. The mammary glands of cattle are optimal tissues to produce therapeutic proteins that cannot be produced in large amounts in traditional systems based on microorganisms and eukaryotic cells. In this study, two knock-in vectors, pBCTPOKI-6 and pBCTPOKI-10, which target the hTPO gene on the bovine beta-casein locus, were designed to develop cloned transgenic cattle. The pBCTPOKI-6 and pBCTPOKI-10 vectors expressed hTPO protein in culture medium at a concentration of 774 pg/ml and 1,867 pg/ml, respectively. Successfully, two targeted cell clones were obtained from the bovine fibroblasts transfected with the pBCTPOKI-6 vector. Cloned embryos reconstructed with the targeted nuclei showed a lower in vitro developmental competence than those with the wild-type nuclei. After transfer of the cloned embryos into recipients, 7 pregnancies were detected at 40 to 60 days of gestation, but failed to develop to term. The results are the first trial for targeting of a human gene on the bovine milk protein gene locus, providing the potential for a large-scale production of therapeutic proteins in the animal bioreactor system.

• Korean Journal of Animal Reproduction
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• v.23 no.4
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• pp.381-391
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• 1999

During the last 20 years, transgenic animal technology has provided revolutionary new opportunities in many aspects of agriculture and biotechnology. Several gene delivery systems including pronuclear injection, retroviral vectors, sperm vectors, and somatic cell cloning have developed for making transgenic animals. In the future major improvements in transgenic animal generation will be mainly covered by somatic cell cloning technology. Many factors affecting integration frequency and expression of the transgenes should be overcome to facilitate the industrial applications of transgenic technology. Transgenic animal technology has settled down in some areas of the biotechnology, especially the mass production of valuable human proteins and xenotransplantation. In the 21st century animal biotechnology will further contribute to welfare of human being.

• Reproductive and Developmental Biology
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• v.40 no.1
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• pp.7-13
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• 2016

Effectiveness of transgene transfer into genome is crucially concerned in mass production of the bio-pharmaceuticals using genetically modified transgenic animals as a bioreactor. Recently, the mammary gland has been considered as a potential bioreactor for the mass production of the bio-pharmaceuticals, which appears to be capable of appropriate post-translational modifications of recombinant proteins. The mammary gland tissue specific vector system may be helpful in solving serious physiological disturbance problems which have been a major obstacle in successful production of transgenic animals. In this study, to minimize physiological disturbance caused by constitutive over-expression of the exogenous gene, we constructed new retrovirus vector system designed for mammary gland-specific expression of the hEPO gene. Using piggyBac vector system, we designed to express hEPO gene under the control of mammary gland tissue specific and lactogenic hormonal inducible goat ${\beta}$-casein or mouse Whey Acidic Protein (mWAP) promoter. Inducible expression of the hEPO gene was confirmed using RT-PCR and ELISA in the mouse mammary gland cells treated with lactogenic hormone. We expect the vector system may optimize production efficiency of transgenic animal and reduce the risk of global expression of transgene.