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Ralph W. Niven - One of the best experts on this subject based on the ideXlab platform.
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stability of recombinant Consensus Interferon to air jet and ultrasonic nebulization
Journal of Pharmaceutical Sciences, 1995Co-Authors: Tsutomu Arakawa, Helen Silvers, Charles M. Ransone, Ralph W. NivenAbstract:The stability of recombinant Consensus α‐Interferon (rConIFN) to air‐jet and ultrasonic nebulization was evaluated. Volumes of 10 mL of 0.5mg/mL rConIFN in phosphate‐buffered saline (PBS) at pH 6.3 were nebulized with a Collison three‐jet nebulizer at 40 psig (10 L/min) for up to 25 min. The effects of pH (3.0, 6.3, and 9.0), additive (0.1% w/v Tween 80, 0.1% w/v Tween 20, and 1% w/v PEG 8000), and ionic strength (0, 0.25, and 1.0) were examined. The effects of ultrasonic nebulization were studied using three devices (DeVilbiss “Aerosonic”; Mountain Medical “Microstat”, and Medix “Easimist”). Stability of rConIFN was assessed by size exclusion chromatography and native and sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE). Structural effects were examined by circular dichroism spectroscopy and bioactivity was assessed by an in vitro mitogenic inhibition bioassay. rConIFN is destabilized by air‐jet nebulization. Insoluble noncovalent aggregates are produced rapidly, and only ≈ 25% of the initial monomeric protein remains after 25 min of nebulization. This correlates with a decrease in in vitro bioactivity. Aggregation during nebulization is influenced by pH (9.0 25% aggregation is observed. Ionic strength does not appear to influence aggregation. rConIFN is also seen to adhere to glass after nebulization. Samples from a rinse of the emptied reservoir with 0.1% w/v SDS, after thorough rinsing with water (three times), show a strong rConIFN band on SDS–PAGE gels. The use of PEG 8000 and Tween mitigate aggregate formation and adhesion (< 20%). The cumulative output collected as a wet or dry aerosol is not aggregated to the same extent as the residual protein remaining in the nebulizer. Ultrasonic nebulization also results in aggregation, but the extent of denaturation is dependent upon the nebulizer used and is related to the heating of nebulizer solutions. Cooling of the nebulizer solution during operation (< 30 °C) minimizes aggregation (< 5%), and bioactivity is retained.
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Systemic Absorption and Activity of Recombinant Consensus Interferons After Intratracheal Instillation and Aerosol Administration
Pharmaceutical research, 1995Co-Authors: Ralph W. Niven, K. Lane Whitcomb, Melissa Woodward, Jennifer Liu, Concesa JornacionAbstract:Purpose. The pulmonary pharmacokinetics and bioactivity of E. coli derived recombinant Consensus Interferon (CIFN) and a modified lactose-conjugated Consensus Interferon (LacCIFN) were evaluated in animals.
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Stability of Recombinant Consensus Interferon to Air‐Jet and Ultrasonic Nebulization
Journal of pharmaceutical sciences, 1995Co-Authors: Tsutomu Arakawa, Helen Silvers, Charles M. Ransone, Ralph W. NivenAbstract:The stability of recombinant Consensus α‐Interferon (rConIFN) to air‐jet and ultrasonic nebulization was evaluated. Volumes of 10 mL of 0.5mg/mL rConIFN in phosphate‐buffered saline (PBS) at pH 6.3 were nebulized with a Collison three‐jet nebulizer at 40 psig (10 L/min) for up to 25 min. The effects of pH (3.0, 6.3, and 9.0), additive (0.1% w/v Tween 80, 0.1% w/v Tween 20, and 1% w/v PEG 8000), and ionic strength (0, 0.25, and 1.0) were examined. The effects of ultrasonic nebulization were studied using three devices (DeVilbiss “Aerosonic”; Mountain Medical “Microstat”, and Medix “Easimist”). Stability of rConIFN was assessed by size exclusion chromatography and native and sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE). Structural effects were examined by circular dichroism spectroscopy and bioactivity was assessed by an in vitro mitogenic inhibition bioassay. rConIFN is destabilized by air‐jet nebulization. Insoluble noncovalent aggregates are produced rapidly, and only ≈ 25% of the initial monomeric protein remains after 25 min of nebulization. This correlates with a decrease in in vitro bioactivity. Aggregation during nebulization is influenced by pH (9.0 25% aggregation is observed. Ionic strength does not appear to influence aggregation. rConIFN is also seen to adhere to glass after nebulization. Samples from a rinse of the emptied reservoir with 0.1% w/v SDS, after thorough rinsing with water (three times), show a strong rConIFN band on SDS–PAGE gels. The use of PEG 8000 and Tween mitigate aggregate formation and adhesion (< 20%). The cumulative output collected as a wet or dry aerosol is not aggregated to the same extent as the residual protein remaining in the nebulizer. Ultrasonic nebulization also results in aggregation, but the extent of denaturation is dependent upon the nebulizer used and is related to the heating of nebulizer solutions. Cooling of the nebulizer solution during operation (< 30 °C) minimizes aggregation (< 5%), and bioactivity is retained.
Siliang Zhang - One of the best experts on this subject based on the ideXlab platform.
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High efficient production of recombinant human Consensus Interferon mutant in high cell density culture of Pichia pastoris using two phases methanol control
Process Biochemistry, 2011Co-Authors: Ju Chu, Yu-you Hao, Yonghong Wang, Yingping Zhuang, Siliang ZhangAbstract:Abstract A recombinant human Consensus Interferon mutant (cIFN) producing Mut+ Pichia pastoris strain was used to study the influence of the methanol concentration on the cIFN production level and quality. The data showed that a high methanol concentration at initial induction phase was important for the expression level, while the specific growth was critical for the cIFN product quality at following induction phase. A high cell density fed-batch culture was performed by two phases methanol control, which composed of 5 g L−1 methanol at initial 6 h induction (the first induction phase) and maintaining of 0.02 h−1 specific growth rate (the second induction phase) by controlling methanol concentration at 0.25%, yielding high cIFN product level with the high quality. Our results indicated that it preferred to produce cIFN doublets containing incomplete disulfide bond and cIFN aggregates when higher methanol concentration was maintained at second induction phase. Chemostat cultures indicated that the formation of disulfide bonds in cIFN was strongly growth-dependent, and cIFN aggregates were easily induced at high specific growth rate. These results provide insights into how cell growth rate could affect the recombinant protein quality, indicating the importance of application of a physiologically suitable strategy.
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Influence of methanol concentration on purification recovery of Consensus Interferon-a produced by Pichia pastoris
Sheng wu gong cheng xue bao = Chinese journal of biotechnology, 2011Co-Authors: Ju Chu, Yonghong Wang, Yingping Zhuang, Siliang ZhangAbstract:We observed the influence of methanol concentration on purification recovery of recombinant human Consensus Interferon-a (cIFN) produced by Pichia pastoris. Fermentations controlled at 0.75% (W/V) methanol showed a 24% increase in clFN expression compared to using 0.25% methanol. However, the purification recovery rate of cIFN at 0.25% methanol was 3.75-fold higher than that at 0.75% methanol. To seek the reason, we analyzed the stability of clFN by SDS-PAGE and Native-PAGE as well as Western blotting. The electrophoresis results revealed that cIFN formed a lot of aggregates in media when the induction was controlled at 0.75% methanol, and two different aggregate forms were found: disulfide bond covalent aggregates and non-covalent aggregates. However, these aggregates almost disappeared when the methanol concentration was controlled at 0.25%, at the same time, cIFN bioactivity of supernatant increased almost 4.48-fold. Finally, 0.73g monomer cIFN was obtained after purification from 1 liter supernatant at 0.25% methanol induction, showed a 2.84-fold increase compare to the induction at 0.75% methanol.
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Incomplete formation of intramolecular disulfide bond triggers degradation and aggregation of human Consensus Interferon-α mutant by Pichia pastoris
Applied microbiology and biotechnology, 2009Co-Authors: Yu-you Hao, Ju Chu, Yonghong Wang, Yingping Zhuang, Siliang ZhangAbstract:Previous study has shown that the degradation and aggregation of recombinant human Consensus Interferon-alpha mutant (cIFN) were serious when cIFN was secreted to bioreactor by Pichia pastoris. In this study, we showed that this phenomenon was concomitant well with the formation of the doublets of cIFN monomers that could be seen clearly on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The doublets were a mixture of two isomers formed by cIFN with different disulfide bonds and identified that the upper cIFN in doublets contains only one disulfide bond while the lower cIFN contains intact disulfide bonds by a novel method termed protein laddering map on SDS-PAGE. In addition, the instability of cIFN with different disulfide bond forms is also analyzed through a novel in vitro conversion assay based on incubation with different concentrations of beta-mercaptoethanol. The results showed that only a wound such as cleavage of only one disulfide bond could be fatal to cIFN stability. If the disulfide bonds in cIFN monomers were broken, three kinds of aggregates would be formed easily: covalent aggregates, non-covalent aggregates, and unknown dimers. Likewise, the unfolded species also displayed reduced stability to proteolysis. These results indicate that the incomplete formation of disulfide bond in cIFN secreted to fermentation broth triggers severe degradation and aggregation of cIFN, which result in sharp decrease of bioactivity of cIFN in bioreactor.
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inhibition of degradation and aggregation of recombinant human Consensus Interferon α mutant expressed in pichia pastoris with complex medium in bioreactor
Applied Microbiology and Biotechnology, 2008Co-Authors: Yu-you Hao, Ju Chu, Yingping Zhuang, Siliang ZhangAbstract:The methylotrophic yeast Pichia pastoris has been used for the expression of many proteins. However, limitations such as protein degradation and aggregation became obvious when secreting heterologous protein-recombinant human Consensus Interferon-α mutant. Here, we investigate the effect of induction temperature on the yield and stability of Interferon mutant expressed by P. patoris with buffered complex medium. The best results in terms of Interferon mutant bioactivity and specific bioactivity were obtained when the microorganism was induced at 15°C, which were 2.91 × 108 ± 0.3 × 108 and 2.26 × 108 ± 0.23 × 108 IU mg−1, respectively. At the same time, the cells grew fast owing to high AOX1-specific activity, and Interferon mutant expression level reached 1.23 g l−1, which was almost 30 times higher than that in the flask. Also, the proteolytic degradation of Interferon mutant was inhibited completely because of lower protease bioactivity probably due to a reduced cell death rate at lower temperatures as well as protection of yeast extract and peptone in complex medium. In addition, Interferon mutant aggregation was repressed significantly by the addition of Tween-80, and a specific bioactivity of 7.35 × 108 ± 0.56 × 108 IU mg−1 was obtained. These results should be applicable to other low-stability recombinant proteins expressed in P. pastoris.
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Inhibition of degradation and aggregation of recombinant human Consensus Interferon-α mutant expressed in Pichia pastoris with complex medium in bioreactor
Applied microbiology and biotechnology, 2008Co-Authors: Yu-you Hao, Ju Chu, Yingping Zhuang, Siliang ZhangAbstract:The methylotrophic yeast Pichia pastoris has been used for the expression of many proteins. However, limitations such as protein degradation and aggregation became obvious when secreting heterologous protein-recombinant human Consensus Interferon-alpha mutant. Here, we investigate the effect of induction temperature on the yield and stability of Interferon mutant expressed by P. patoris with buffered complex medium. The best results in terms of Interferon mutant bioactivity and specific bioactivity were obtained when the microorganism was induced at 15 degrees C, which were 2.91 x 10(8) +/- 0.3 x 10(8) and 2.26 x 10(8 )+/- 0.23 x 10(8) IU mg(-1), respectively. At the same time, the cells grew fast owing to high AOX1-specific activity, and Interferon mutant expression level reached 1.23 g l(-1), which was almost 30 times higher than that in the flask. Also, the proteolytic degradation of Interferon mutant was inhibited completely because of lower protease bioactivity probably due to a reduced cell death rate at lower temperatures as well as protection of yeast extract and peptone in complex medium. In addition, Interferon mutant aggregation was repressed significantly by the addition of Tween-80, and a specific bioactivity of 7.35 x 10(8) +/- 0.56 x 10(8) IU mg(-1) was obtained. These results should be applicable to other low-stability recombinant proteins expressed in P. pastoris.
Tsutomu Arakawa - One of the best experts on this subject based on the ideXlab platform.
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Comparison of an antiviral activity of recombinant Consensus Interferon with recombinant Interferon-α-2b
Microbes and Infection, 1999Co-Authors: A. Hajime Koyama, Tsutomu Arakawa, Akio AdachiAbstract:Abstract To avoid possible uncertainty in comparing biological activities of Interferon samples from different sources where Interferon concentrations were determined independently, we prepared chromatographically pure preparations of Consensus Interferon and Interferon-α-2b (one of the two commercially available recombinant alpha Interferons). We revealed that Consensus Interferon has a stronger antiviral activity than Interferon-α-2b, although the effects of these two recombinant Interferons on the cellular macromolecule synthesis are at similar levels.
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stability of recombinant Consensus Interferon to air jet and ultrasonic nebulization
Journal of Pharmaceutical Sciences, 1995Co-Authors: Tsutomu Arakawa, Helen Silvers, Charles M. Ransone, Ralph W. NivenAbstract:The stability of recombinant Consensus α‐Interferon (rConIFN) to air‐jet and ultrasonic nebulization was evaluated. Volumes of 10 mL of 0.5mg/mL rConIFN in phosphate‐buffered saline (PBS) at pH 6.3 were nebulized with a Collison three‐jet nebulizer at 40 psig (10 L/min) for up to 25 min. The effects of pH (3.0, 6.3, and 9.0), additive (0.1% w/v Tween 80, 0.1% w/v Tween 20, and 1% w/v PEG 8000), and ionic strength (0, 0.25, and 1.0) were examined. The effects of ultrasonic nebulization were studied using three devices (DeVilbiss “Aerosonic”; Mountain Medical “Microstat”, and Medix “Easimist”). Stability of rConIFN was assessed by size exclusion chromatography and native and sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE). Structural effects were examined by circular dichroism spectroscopy and bioactivity was assessed by an in vitro mitogenic inhibition bioassay. rConIFN is destabilized by air‐jet nebulization. Insoluble noncovalent aggregates are produced rapidly, and only ≈ 25% of the initial monomeric protein remains after 25 min of nebulization. This correlates with a decrease in in vitro bioactivity. Aggregation during nebulization is influenced by pH (9.0 25% aggregation is observed. Ionic strength does not appear to influence aggregation. rConIFN is also seen to adhere to glass after nebulization. Samples from a rinse of the emptied reservoir with 0.1% w/v SDS, after thorough rinsing with water (three times), show a strong rConIFN band on SDS–PAGE gels. The use of PEG 8000 and Tween mitigate aggregate formation and adhesion (< 20%). The cumulative output collected as a wet or dry aerosol is not aggregated to the same extent as the residual protein remaining in the nebulizer. Ultrasonic nebulization also results in aggregation, but the extent of denaturation is dependent upon the nebulizer used and is related to the heating of nebulizer solutions. Cooling of the nebulizer solution during operation (< 30 °C) minimizes aggregation (< 5%), and bioactivity is retained.
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Stability of Recombinant Consensus Interferon to Air‐Jet and Ultrasonic Nebulization
Journal of pharmaceutical sciences, 1995Co-Authors: Tsutomu Arakawa, Helen Silvers, Charles M. Ransone, Ralph W. NivenAbstract:The stability of recombinant Consensus α‐Interferon (rConIFN) to air‐jet and ultrasonic nebulization was evaluated. Volumes of 10 mL of 0.5mg/mL rConIFN in phosphate‐buffered saline (PBS) at pH 6.3 were nebulized with a Collison three‐jet nebulizer at 40 psig (10 L/min) for up to 25 min. The effects of pH (3.0, 6.3, and 9.0), additive (0.1% w/v Tween 80, 0.1% w/v Tween 20, and 1% w/v PEG 8000), and ionic strength (0, 0.25, and 1.0) were examined. The effects of ultrasonic nebulization were studied using three devices (DeVilbiss “Aerosonic”; Mountain Medical “Microstat”, and Medix “Easimist”). Stability of rConIFN was assessed by size exclusion chromatography and native and sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE). Structural effects were examined by circular dichroism spectroscopy and bioactivity was assessed by an in vitro mitogenic inhibition bioassay. rConIFN is destabilized by air‐jet nebulization. Insoluble noncovalent aggregates are produced rapidly, and only ≈ 25% of the initial monomeric protein remains after 25 min of nebulization. This correlates with a decrease in in vitro bioactivity. Aggregation during nebulization is influenced by pH (9.0 25% aggregation is observed. Ionic strength does not appear to influence aggregation. rConIFN is also seen to adhere to glass after nebulization. Samples from a rinse of the emptied reservoir with 0.1% w/v SDS, after thorough rinsing with water (three times), show a strong rConIFN band on SDS–PAGE gels. The use of PEG 8000 and Tween mitigate aggregate formation and adhesion (< 20%). The cumulative output collected as a wet or dry aerosol is not aggregated to the same extent as the residual protein remaining in the nebulizer. Ultrasonic nebulization also results in aggregation, but the extent of denaturation is dependent upon the nebulizer used and is related to the heating of nebulizer solutions. Cooling of the nebulizer solution during operation (< 30 °C) minimizes aggregation (< 5%), and bioactivity is retained.
Yu-you Hao - One of the best experts on this subject based on the ideXlab platform.
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High efficient production of recombinant human Consensus Interferon mutant in high cell density culture of Pichia pastoris using two phases methanol control
Process Biochemistry, 2011Co-Authors: Ju Chu, Yu-you Hao, Yonghong Wang, Yingping Zhuang, Siliang ZhangAbstract:Abstract A recombinant human Consensus Interferon mutant (cIFN) producing Mut+ Pichia pastoris strain was used to study the influence of the methanol concentration on the cIFN production level and quality. The data showed that a high methanol concentration at initial induction phase was important for the expression level, while the specific growth was critical for the cIFN product quality at following induction phase. A high cell density fed-batch culture was performed by two phases methanol control, which composed of 5 g L−1 methanol at initial 6 h induction (the first induction phase) and maintaining of 0.02 h−1 specific growth rate (the second induction phase) by controlling methanol concentration at 0.25%, yielding high cIFN product level with the high quality. Our results indicated that it preferred to produce cIFN doublets containing incomplete disulfide bond and cIFN aggregates when higher methanol concentration was maintained at second induction phase. Chemostat cultures indicated that the formation of disulfide bonds in cIFN was strongly growth-dependent, and cIFN aggregates were easily induced at high specific growth rate. These results provide insights into how cell growth rate could affect the recombinant protein quality, indicating the importance of application of a physiologically suitable strategy.
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Incomplete formation of intramolecular disulfide bond triggers degradation and aggregation of human Consensus Interferon-α mutant by Pichia pastoris
Applied microbiology and biotechnology, 2009Co-Authors: Yu-you Hao, Ju Chu, Yonghong Wang, Yingping Zhuang, Siliang ZhangAbstract:Previous study has shown that the degradation and aggregation of recombinant human Consensus Interferon-alpha mutant (cIFN) were serious when cIFN was secreted to bioreactor by Pichia pastoris. In this study, we showed that this phenomenon was concomitant well with the formation of the doublets of cIFN monomers that could be seen clearly on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The doublets were a mixture of two isomers formed by cIFN with different disulfide bonds and identified that the upper cIFN in doublets contains only one disulfide bond while the lower cIFN contains intact disulfide bonds by a novel method termed protein laddering map on SDS-PAGE. In addition, the instability of cIFN with different disulfide bond forms is also analyzed through a novel in vitro conversion assay based on incubation with different concentrations of beta-mercaptoethanol. The results showed that only a wound such as cleavage of only one disulfide bond could be fatal to cIFN stability. If the disulfide bonds in cIFN monomers were broken, three kinds of aggregates would be formed easily: covalent aggregates, non-covalent aggregates, and unknown dimers. Likewise, the unfolded species also displayed reduced stability to proteolysis. These results indicate that the incomplete formation of disulfide bond in cIFN secreted to fermentation broth triggers severe degradation and aggregation of cIFN, which result in sharp decrease of bioactivity of cIFN in bioreactor.
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inhibition of degradation and aggregation of recombinant human Consensus Interferon α mutant expressed in pichia pastoris with complex medium in bioreactor
Applied Microbiology and Biotechnology, 2008Co-Authors: Yu-you Hao, Ju Chu, Yingping Zhuang, Siliang ZhangAbstract:The methylotrophic yeast Pichia pastoris has been used for the expression of many proteins. However, limitations such as protein degradation and aggregation became obvious when secreting heterologous protein-recombinant human Consensus Interferon-α mutant. Here, we investigate the effect of induction temperature on the yield and stability of Interferon mutant expressed by P. patoris with buffered complex medium. The best results in terms of Interferon mutant bioactivity and specific bioactivity were obtained when the microorganism was induced at 15°C, which were 2.91 × 108 ± 0.3 × 108 and 2.26 × 108 ± 0.23 × 108 IU mg−1, respectively. At the same time, the cells grew fast owing to high AOX1-specific activity, and Interferon mutant expression level reached 1.23 g l−1, which was almost 30 times higher than that in the flask. Also, the proteolytic degradation of Interferon mutant was inhibited completely because of lower protease bioactivity probably due to a reduced cell death rate at lower temperatures as well as protection of yeast extract and peptone in complex medium. In addition, Interferon mutant aggregation was repressed significantly by the addition of Tween-80, and a specific bioactivity of 7.35 × 108 ± 0.56 × 108 IU mg−1 was obtained. These results should be applicable to other low-stability recombinant proteins expressed in P. pastoris.
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Inhibition of degradation and aggregation of recombinant human Consensus Interferon-α mutant expressed in Pichia pastoris with complex medium in bioreactor
Applied microbiology and biotechnology, 2008Co-Authors: Yu-you Hao, Ju Chu, Yingping Zhuang, Siliang ZhangAbstract:The methylotrophic yeast Pichia pastoris has been used for the expression of many proteins. However, limitations such as protein degradation and aggregation became obvious when secreting heterologous protein-recombinant human Consensus Interferon-alpha mutant. Here, we investigate the effect of induction temperature on the yield and stability of Interferon mutant expressed by P. patoris with buffered complex medium. The best results in terms of Interferon mutant bioactivity and specific bioactivity were obtained when the microorganism was induced at 15 degrees C, which were 2.91 x 10(8) +/- 0.3 x 10(8) and 2.26 x 10(8 )+/- 0.23 x 10(8) IU mg(-1), respectively. At the same time, the cells grew fast owing to high AOX1-specific activity, and Interferon mutant expression level reached 1.23 g l(-1), which was almost 30 times higher than that in the flask. Also, the proteolytic degradation of Interferon mutant was inhibited completely because of lower protease bioactivity probably due to a reduced cell death rate at lower temperatures as well as protection of yeast extract and peptone in complex medium. In addition, Interferon mutant aggregation was repressed significantly by the addition of Tween-80, and a specific bioactivity of 7.35 x 10(8) +/- 0.56 x 10(8) IU mg(-1) was obtained. These results should be applicable to other low-stability recombinant proteins expressed in P. pastoris.
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The inhibition of aggregation of recombinant human Consensus Interferon-α mutant during Pichia pastoris fermentation
Applied microbiology and biotechnology, 2006Co-Authors: Yu-you Hao, Ju Chu, Yonghong Wang, Yingping Zhuang, Siliang ZhangAbstract:Lower induction temperature and polyoxyethylene sorbitan monolaurate (Tween-20) were successfully used to inhibit the aggregation of recombinant human Consensus Interferon-alpha mutant (cIFN) during Pichia pastoris fermentation. When the induction temperature was decreased from 30 to 20 degrees C, the cIFN secreted into the medium was in the form of monomers instead of aggregates. The maximum specific activity at 20 degrees C was 4.04 times as high as that at 30 degrees C. There was no obvious effect on the cell growth at 20 degrees C, but the total protein level was decreased. Similar inhibition effect on cIFN aggregation was observed when 0.2 g l(-1) Tween-20 was added during induction. Furthermore, there was a synergistic effect found between induction temperature and Tween-20 on the inhibition of cIFN aggregation. The maximum specific activity with Tween-20 at 20 degrees C was 19.9-fold higher than that without Tween-20 at 30 degrees C.
Alexander Monto - One of the best experts on this subject based on the ideXlab platform.
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Retreatment of Hepatitis C with Consensus Interferon and Ribavirin After Nonresponse or Relapse to Pegylated Interferon and Ribavirin: A National VA Clinical Practice Study
Digestive Diseases and Sciences, 2011Co-Authors: Helen S. Yee, Kathryn Tortorice, Myrna L. Cozen, Hui Shen, Summer Chapman, Fran Cunningham, Sue L. Currie, Alexander MontoAbstract:Background Studies of the retreatment with Consensus Interferon (CIFN) and ribavirin (RBV) of hepatitis C virus (HCV)-infected patients who failed prior pegylated Interferon alfa/ribavirin (PEG-IFN/RBV) have found quite variable efficacy and tolerability of this therapy. As such, CIFN/RBV use and efficacy in clinical practice were evaluated within the Department of Veterans Affairs (VA), the largest national, integrated system for HCV care. Aims The purpose of this study was to determine rates of sustained virologic response (SVR) and patterns of CIFN/RBV use in the VA. Methods included retrospective review of national VA data in HCV-infected patients who had previously failed ≥12 weeks of PEG-IFN/RBV and were prescribed CIFN/RBV between October 1, 2003 and September 30, 2006. Results A total of 597 patients met the study criteria. CIFN was primarily dosed as 15 mcg subcutaneously daily combined with standard doses of RBV. Mean treatment duration was 21 weeks; CIFN was discontinued within 4 weeks in 24%. Hematological growth factors were used in 49%. Post-treatment viral loads were available in 385 patients. SVR to CIFN/RBV was achieved in 11%, and was significantly higher in prior PEG-IFN/RBV relapsers compared with nonresponders (31% vs. 6%, respectively; P
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Retreatment of hepatitis C with Consensus Interferon and ribavirin after nonresponse or relapse to pegylated Interferon and ribavirin: a national VA clinical practice study.
Digestive diseases and sciences, 2011Co-Authors: Helen S. Yee, Sue Currie, Kathryn Tortorice, Myrna L. Cozen, Hui Shen, Summer Chapman, Fran Cunningham, Alexander MontoAbstract:Background Studies of the retreatment with Consensus Interferon (CIFN) and ribavirin (RBV) of hepatitis C virus (HCV)-infected patients who failed prior pegylated Interferon alfa/ribavirin (PEG-IFN/RBV) have found quite variable efficacy and tolerability of this therapy. As such, CIFN/RBV use and efficacy in clinical practice were evaluated within the Department of Veterans Affairs (VA), the largest national, integrated system for HCV care.