In Seop Kim

Hannam University, Daiden, Daejeon, South Korea

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Publications (35)

  • In Seop Kim · Jung Eun Bae · Sang Eun Han · [...] · Hana Kim
    Article · Jul 2016 · New Biotechnology
  • Dong-Myong Kim · Ho-Chang Kang · Hyung-Joon Cha · [...] · In Seop Kim
    Article · Jun 2016 · Korean Journal of Microbiology
  • Woon Young Ko · Na Gyeong Noh · In Seop Kim
    [Show abstract] [Hide abstract] ABSTRACT: Biologics and medical devices manufactured with bovine-derived raw materials have the risk of viral contamination. Therefore, viral validation study is essential to ensure the safety of the products. Bovine adenovirus type-1 (BAdV-1) is one of the common bovine viral pathogens. For quantitative detection of BAdV-1 during the manufacture of biologics and medical devices, a TaqMan probe real-time PCR method was developed. Specific primers and TaqMan probe for amplifying and detecting BAdV-1 DNA were designed. Specificity, limit of detection (LOD), and robustness of the method was validated according to international guideline on the validation of nucleic acid amplification tests for the pathogen detection. The sensitivity of the assay was found to be 7.44 × 101 TCID50/ml. The real-time PCR method was reproducible, very specific to BAdV-1, and robust. Moreover, the method was successfully applied to the validation of Chinese Hamster Ovary (CHO)-K1 cells artificially infected with BAdV-1, a commercial CHO master bank, and bovine type 1 collagen. The overall results indicate that this rapid, specific, sensitive, and robust assay can be reliably used for quantitative detection of BAdV-1 contamination during the manufacture of biologics and medical devices using bovine-derived raw materials.
    Article · Sep 2015 · Korean Journal of Microbiology
  • Jae Il Lee · In Seop Kim
    Article · Oct 2014
  • Mushik Park · Sungpo Kim · In Seop Kim · Daegu Son
    Dataset · Jun 2014
  • Article · Feb 2014
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: The extract from Lysimachia foenum-graecum (LFE) has been known to possess various instructive characters including anti-oxidant, anti-obesity, fungicidal activities. However, the accurate mechanism of those effects of LFE is not well known. In that respect, we evaluated the apoptotic effect and anti-cancer efficacy of extracts of LFE in MCF-7 breast cancer cells. In this study, we hypothesized that LFE may exert cancer cell apoptosis through regulating p53 and mitochondria-mediated apoptotic proteins. And this substance can generate ROS to cause free radical-induced apoptosis. Accordingly, the generation of ROS by LFE triggers the activation of p53 which are accompanied by pro-apoptotic protein activation and suppression of pro-survival proteins. We determined with MTT assay, flow cytometry for detection of intracellular ROS and Annexin V-PI staining, Western blotting. Consequently, our researches demonstrated that the treatment of LFE to breast cancer cells resulted in an activation of p53, Puma, Bax, cleaved-PARP and an inhibition of Bcl-2 expressions.
    Full-text Article · Oct 2013
  • Kye Joon Lee · Sung Gyun Kang · In Seop Kim
    Article · Jan 2013
  • Jung Eun Bae · Chan Kyung Kim · Sungpo Kim · [...] · In Seop Kim
    [Show abstract] [Hide abstract] ABSTRACT: Most types of collagen used for biomedical applications, such as cell therapy and tissue engineering, are derived from animal tissues. Therefore, special precautions must be taken during the production of these proteins in order to assure against the possibility of the products transmitting infectious diseases to the recipients. The ability to remove and/or inactivate known and potential viral contaminants during the manufacturing process is an ever-increasingly important parameter in assessing the safety of biomedical products. The purpose of this study was to evaluate the efficacies of the 70% ethanol treatment and pepsin treatment at pH 2.0 for the inactivation of bovine viruses during the manufacture of collagen type I from bovine hides. A variety of experimental model viruses for bovine viruses including bovine herpes virus (BHV), bovine viral diarrhea virus (BVDV), bovine parainfluenza 3 virus (BPIV-3), and bovine parvovirus (BPV), were chosen for the evaluation of viral inactivation efficacy. BHV, BVDV, BPIV-3, and BPV were effectively inactivated to undetectable levels within 1 h of 70% ethanol treatment for 24 h, with log reduction factors of , , , and , respectively. BHV, BVDV, BPIV-3, and BPV were also effectively inactivated to undetectable levels within 5 days of pepsin treatment for 14 days, with the log reduction factors of , , , and , respectively. The cumulative virus reduction factors of BHV, BVDV, BPIV-3, and BPV were , , , and . These results indicate that the production process for collagen type I from bovine hides has a sufficient virus-reducing capacity to achieve a high margin of virus safety.
    Article · Dec 2012 · Korean Journal of Microbiology
  • Jung Eun Bae · In Seop Kim
    [Show abstract] [Hide abstract] ABSTRACT: Validation of viral safety is essential in ensuring the safety of mammalian cell culture-derived biopharmaceuticals since numerous adventitious viruses get contaminated during the manufacturing process. In particular, Chinese hamster ovary (CHO) cells are highly susceptible to minute virus of mice (MVM), bovine parvovirus (BPV), and bovine herpesvirus (BHV). Therefore, viral detection during CHO cell culturing is necessary to ensure the safety of biopharmaceuticals against viruses. In this study, a multiplex PCR assay was developed and subsequently evaluated for its effectiveness to simultaneously detect MVM, BPV and BHV during the manufacture of cell culture-derived biopharmaceuticals. Specific primers for MVM, BPV, and BHV were selected, and a multiplex PCR was optimized. The sensitivity of the assay was 6.49 × 101 TCID50/mL for MVM, 7.23 × 102 TCID50/mL for BPV, and 5.80 × 101 TCID50/mL for BHV. The multiplex PCR assay was very specific to MVM, BPV, and BHV and was subsequently applied to the validation of CHO cells artificially infected with each virus. It could detect each viral DNA from CHO cells as well as culture supernatants. Therefore, we concluded that the multiplex PCR assay is invaluable for detecting adventitious viruses during the manufacture of cell culture-derived biopharmaceuticals. Keywordsmultiplex PCR–CHO cell–minute virus of mice–bovine parvovirus–bovine herpesvirus
    Article · Dec 2011 · Biotechnology and Bioprocess Engineering
  • Eun Kyo Jeong · Hark Mo Sung · In Seop Kim
    [Show abstract] [Hide abstract] ABSTRACT: Although transmission of pandemic influenza A virus H1N1 2009 is still occurring globally, little has been reported about how this outbreak has affected the safety of plasma derivatives. To evaluate the safety of plasma derivatives, dedicated virus clearance processes used during their production were investigated for their effectiveness in eliminating this virus of recent concern. In this study, influenza A virus H1N1 strain A/NWS/33 (H1N1) was chosen as a surrogate. H1N1 was completely inactivated by fraction IV fractionation as well as pasteurization during the manufacture of albumin. H1N1 was also effectively removed into the precipitate by fraction III fractionation and completely inactivated by low pH incubation as well as pasteurization during the manufacture of intravenous immunoglobulin. H1N1 was completely inactivated within 1 min of solvent/detergent treatment using 0.3% tri (n-butyl) phosphate and 1.0% Triton X-100 and also completely inactivated within 10 min of dry-heat treatment at 98 °C during the manufacture of factor VIII. H1N1 was completely removed by virus filtration process using Viresolve NFP filter and also completely inactivated by pasteurization during the manufacture of anti-thrombin III. These results indicate that all the virus clearance processes commonly used have sufficient H1N1 reducing capacity to achieve a high margin of safety.
    Article · Nov 2010 · Biologicals
  • Jung Eun Bae · Eun Kyo Jeong · Jae Il Lee · [...] · In Seop Kim
    Article · Nov 2010 · Journal of Biotechnology
  • Jung Eun Bae · Eun Kyo Jeong · Jae Il Lee · [...] · In Seop Kim
    Article · Nov 2010 · Journal of Biotechnology
  • Dong Hyuck Lee · Jung Eun Bae · Jung Hee Lee · [...] · In Seop Kim
    [Show abstract] [Hide abstract] ABSTRACT: E. coli has been widely used as a host system to manufacture recombinant proteins for human therapeutic use. Among impurities to be eliminated during the downstream process, residual host cell DNA is a major interest for safety. Residual E. coli host cell DNA in the final products are usually determined using conventional slot blot hybridization assay or total DNA Threshold assay, although these methods are time consuming, expensive, and relatively insensitive. Therefore a sensitive real-time PCR assay for specific detection of residual E. coli DNA was developed and compared with slot blot hybridization assay and Threshold assay to validate the overall capability of these methods. Specific primer pair for amplification of the E. coli 16S rRNA gene was selected to improve the sensitivity, and E. coli host cell DNA was quantified by use of SYBR Green 1. The detection limit of real-time PCR assay in the optimized condition was calculated to be 0.042 pg genomic DNA, which is much higher than those of slot blot hybridization assay and Threshold assay of which detection limit were 2.42 and 3.73 pg genomic DNA, respectively. The real-time PCR assay was validated to be more reproducible, accurate, and precise than slot blot hybridization assay and Threshold assay. The real-time PCR assay may be a useful tool for quantitative detection and clearance validation of residual E. coli DNA during the manufacturing process for recombinant therapeutics.
    Article · Oct 2010 · Journal of Microbiology and Biotechnology
  • Eun Kyo Jeong · Jung Eun Bae · In Seop Kim
    [Show abstract] [Hide abstract] ABSTRACT: Because any patient, health care worker, or visitor is capable of transmitting influenza to susceptible persons within hospitals, hospital-acquired influenza has been a clinical concern. Disinfection and cleaning of medical equipment, surgical instruments, and hospital environment are important measures to prevent transmission of influenza virus from hospitals to individuals. This study was conducted to evaluate the efficacy of disinfection processes, which can be easily operated at hospitals, in inactivating influenza A virus H1N1 (H1N1). The effects of 0.1 mol/L NaOH, 70% ethanol, 70% 1-propanol, solvent/detergent (S/D) using 0.3% tri (n-butyl)-phosphate and 1.0% Triton X-100, heat, and ethylene oxide (EO) treatments in inactivating H1N1 were determined. Inactivation of H1N1 was kinetically determined by the treatment of disinfectants to virus solution. Also, a surface test method, which involved drying an amount of virus on a surface and then applying the inactivation methods for 1 minute of contact time, was used to determine the virucidal activity. H1N1 was completely inactivated to undetectable levels in 1 minute of 70% ethanol, 70% 1-propanol, and solvent/detergent treatments in the surface tests as well as in the suspension tests. H1N1 was completely inactivated in 1 minute of 0.1 mol/L NaOH treatment in the suspension tests and also effectively inactivated in the surface tests with the log reduction factor of 3.7. H1N1 was inactivated to undetectable levels within 5 minutes, 2.5 minutes, and 1 minute of heat treatment at 70, 80, and 90 degrees C, respectively in the suspension tests. Also, H1N1 was completely inactivated by EO treatment in the surface tests. Common disinfectants, heat, and EO tested in this study were effective at inactivating H1N1. These results would be helpful in implementing effective disinfecting measures to prevent hospital-acquired infections.
    Article · Jun 2010 · American journal of infection control
  • Source
    Deok Ja Oh · Yoo La Lee · Jae Won Kang · [...] · In Seop Kim
    [Show abstract] [Hide abstract] ABSTRACT: The safety of plasma derivatives has been reinforced since 1980s by variable pathogen inactivation or elimination techniques. Nucleic acid amplification test (NAT) for the source plasma has also been implemented worldwide. Recently nanofiltration has been used in some country for ensuring safety of plasma derivatives to eliminate non-enveloped viruses such as parvovirus B19 (B19V) and hepatitis A virus (HAV). We evaluated the efficacy of nanofiltration for the elimination of B19V and HAV. To verify the efficacy of nanofiltration, we adopted a 20 nm Viresolve NFP (Millipore, USA) in the scaling down (1:1,370) model of the antithrombin III production. As virus stock solutions, we used B19V reactive plasma and porcine parvovirus (PPV) and HAV obtained from cell culture. And 50% tissue culture infectious dose was consumed as infectious dose. The methods used to evaluate the virus-elimination efficacy were reverse-transcriptase polymerase chain reaction for B19V and the cytopathic effect calculation after filtration for PPV and HAV. B19V was not detected by RT-PCR in the filtered antithrombin III solutions with initial viral load of 6.42 x 10(5) IU/mL and 1.42 x 10(5) IU/mL before filtration. The virus-elimination efficacy of nanofiltration for PPV and HAV were > or = (3.32) and > or = (3.31), respectively. Nanofiltration would be an effective method for the elimination of B19V and HAV. It may be used as a substitute for NAT screening of these viruses in source plasma to ensure safety of plasma derivatives in Korea.
    Full-text Article · Feb 2010 · The Korean Journal of Laboratory Medicine
  • In Seop Kim · Jung Eun Bae · Hark Mo Sung · [...] · Yong Woon Choi
    [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to evaluate the efficacy and mechanisms of the solvent/detergent (S/D) treatment, DEAE-toyopearl 650M anion-exchange column chromatography, heparin-sepharose 6FF affinity column chromatography, and Viresolve NFP filtration steps employed in the manufacture of high-purity antihemophilic factor IX (Green-Nine VF) from human plasma, with regard to removal and/or inactivation of blood-borne viruses. A variety of experimental model viruses for human pathogenic viruses, including human immunodeficiency virus (HIV), bovine herpes virus (BHV), bovine viral diarrhoea virus (BVDV), hepatitis A virus (HAV), murine encephalomyocarditis virus (EMCV), and porcine parvovirus (PPV), were all selected for this study. Samples from relevant stages of the production process were spiked with each virus and subjected to scale-down processes mimicking the manufacture of high-purity factor IX. Samples were collected at each step, immediately titrated using a 50% tissue culture infectious dose (TCID50), and virus reduction factors were evaluated. S/D treatment using the organic solvent, tri (n-butyl) phosphate (TNBP), and the detergent, Tween 80, was a robust and effective step in inactivation of enveloped viruses. Titers of HIV, BHV, and BVDV were reduced from the initial titer of 6.06, 7.72, and 6.92 log10 TCID50, respectively, reaching undetectable levels within 1 min of S/D treatment. DEAE-toyopearl 650M anion-exchange column chromatography was found to be a moderately effective step in the removal of HAV, EMCV, and PPV with log reduction factors of 1.12, 2.67, and 1.38, respectively. Heparin-sepharose 6FF affinity column chromatography was also moderately effective for partitioning BHV, BVDV, HAV, EMCV, and PPV with log reduction factors of 1.55, 1.35, 1.08, 1.19, and 1.61, respectively. The Viresolve NFP filtration step was a robust and effective step in removing all viruses tested, since HIV, BHV, BVDV, HAV, EMCV, and PPV were completely removed during the filtration step with log reduction factors of ≥ 5.51, ≥ 5.76, ≥ 5.18, ≥ 5.34, ≥ 6.13, and ≥ 4.28, respectively. Cumulative log reduction factors of HIV, BHV, BVDV, HAV, EMCV, and PPV were ≥ 10.52, ≥ 12.07, ≥ 10.49, ≥ 7.54, ≥ 9.99, and ≥ 7.24, respectively. These results indicate that the production process for GreenNine VF has a sufficient virus reduction capacity for achievement of a high margin of virus safety.
    Article · Dec 2009 · Biotechnology and Bioprocess Engineering
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Streptomyces coelicolor produces an extracellular protease inhibitor protein, STI (Streptomyces trypsin inhibitor). We show that post-growth elimination of STI is needed for colonies to develop aerial mycelium efficiently. Inactivation of STI, and thus the normal progression of colony development, at least partly involves an extracellular protease specified by gene SCO5913. Two-hybrid analysis identified two possible targets of STI inhibition (the products of SCO1355 and SCO5447), both extracellular proteases containing a domain homologous with the P-domain of eukaryotic convertases, proteases that mediate the processing of many precursors with important cellular or developmental roles. At least the SCO1355 protease is needed for the normal progression of development. Two components of the proposed cascade are dependent on the tRNA for the rare UUA (leucine) codon, which is specified by the developmental gene bldA. A model is presented that links intracellular regulatory events with an extracellular protease cascade to facilitate normal development.
    Full-text Article · Jan 2009 · Molecular Microbiology
  • Wangyun Won · Kwang Soon Lee · In Seop Kim · [...] · Seokyoung Lee
    [Show abstract] [Hide abstract] ABSTRACT: A model predictive control (MPC) system has been developed for application to the condensate recycle process of a 300 MW cogeneration power station of the East-West Power Plant, Gyeonggido, Korea. Unlike other industrial processes where MPC has been predominantly applied, the operation mode of the cogeneration power station changes continuously with weather and seasonal conditions. Such characteristic makes it difficult to find the process model for controller design through identification. To overcome the difficulty, process models for MPC design were derived for each operation mode from the material balance applied to the pipeline network around the concerned process. The MPC algorithm has been developed so that the controller tuning is easy with one tuning knob for each output and the constrained optimization is solved by an interior-point method. For verification of the MPC system before process implementation, a process simulator was also developed. Performance of the MPC was investigated first with a process simulator against various disturbance scenarios.
    Article · Sep 2008 · Korean Journal of Chemical Engineering
  • In Seop Kim · Yong Woon Choi · Yong Kang · [...] · Yong-Sung Kim
    [Show abstract] [Hide abstract] ABSTRACT: Viral safety is an important prerequisite for clinical preparations of plasma-derived pharmaceuticals. One potential way to increase the safety of therapeutic biological products is the use of a virus-retentive filter. In order to increase the viral safety of human antihemophilic factor IX, particularly in regard to non-enveloped viruses, virus removal process using a polyvinylidene fluoride membrane filter (Viresolve NFP) has been optimized. The most critical factor affecting the filtration efficiency was operating pH and the optimum pH was 6 or 7. Flow rate increased with increasing operating pressure and temperature. Recovery yield in the optimized production-scale process was 96%. No substantial changes were observed in the physical and biochemical characteristics of the filtered factor IX in comparison with those before filtration. A 47-mm disk membrane filter was used to simulate the process performance of the production-scale cartridges and to test if it could remove several experimental model viruses for human pathogenic viruses, including human hepatitis A virus (HAV), porcine parvovirus (PPV), murine encephalomyocarditis virus (EMCV), human immunodeficiency virus type 1 (HIV), bovine viral diarrhea virus (BVDV), and bovine herpes virus (BHV). Nonenveloped viruses (HAV, PPV, and EMCV) as well as enveloped viruses (HIV, BVDV, and BHV) were completely removed during filtration. The log reduction factors achieved were >or=6.12 for HAV, >or=4.28 for PPV, >or=5.33 for EMCV, >or=5.51 for HIV, >or=5.17 for BVDV, and >or=5.75 for BHV. These results indicate that the virus filtration process successfully improved the viral safety of factor IX.
    Article · Aug 2008 · Journal of Microbiology and Biotechnology

Publication Stats

224 Citations

Institutions

  • 2004-2011
    • Hannam University
      • Department of Biological Sciences
      Daiden, Daejeon, South Korea
  • 2005-2006
    • Sogang University
      • Department of Chemical and Biomolecular Engineering
      Sŏul, Seoul, South Korea