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Engineering CELLS,
   Engineering RESPONSES

ANIMAL CELL TECHNOLOGY

High Value, Low Cost of Goods

The market demand for recombinant proteins as therapeutics remains strong in recent years. The higher dosage requirement for antibody drugs has driven the need for efficient, high-titer processes which can dramatically reduce the cost of goods during manufacturing.

The Animal Cell Technology Group has developed Internal Ribosome Entry Site (IRES)-mediated mammalian expression vectors to facilitate the fast and efficient development of stable cell lines that can produce monoclonal antibodies and other recombinant proteins at high titers.

To further improve protein productivity and product yields, chemically defined protein-free media and optimized feeding strategies for recombinant therapeutic protein production using Chinese Hamster Ovary (CHO) and other mammalian cell lines have also been established. Using new technologies such as Metabolomics, intra- and extra-cellular metabolites will be tracked in high density cultures, which can guide media design for improved culture performance.

A bioreactor platform for Influenza virus production using Vero cells has been established to study cell-based processes for the manufacturing of viral vaccines. Microarray and proteomic analyses of high density fed-batch cultures has led to the identification of targets for cell engineering and the generation of anti apoptotic CHO Gene-Targeted (GT) cell lines with extended viabilities and increased recombinant protein titers.

To build on these efforts, genomic, proteomic and metabolomic profiling, as well as studies on microRNA regulation, will be used to identify gene, protein, metabolite and microRNA targets which are commonly expressed in high producer cell lines. These targets can be directed towards cell engineering and rapid cell screening applications.

The group also collaborates with the Stem Cells Group in the production of novel monoclonal antibodies (mAbs) to human embryonic stem cells (hESC) and cancer cell lines using mammalian systems; the Downstream Processing Group in the development of novel biomolecule purification technologies; as well as the Expression Engineering Group in the development of engineered cell lines.

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People

Yuansheng

Dr. Yang Yuansheng

PhD in Chemical Engineering (2005) Vanderbilt University, USA

Research Focus/Interests
  • Vector design, cell line development, cell engineering, and bioprocess development to enhance production of recombinant protein production in mammalian cells

Dr. Ng Say Kong

PhD in Molecular Engineering of Biological and Chemical Systems (2006) National University of Singapore, Singapore

Research Focus/Interests
  • Culture medium and bioreactor process developments to improve the production of biologic products using animal cells
  • Expression vector optimization to improve production cell line development for biologics manufacturing
  • Recombinant protein expression in mammalian cells
  • Production of viral vaccines
Shireen Goh

Dr. Shireen Goh

PhD in Materials Science and Engineering (2013) Massachusetts Institute of Technology (MIT), USA

Research Focus/Interests
  • Bioprocess characterization and monitoring
  • Micro-bioreactor for upstream process development

Dr. Justin Goh

PhD in Clinical Science (2016), University of Queensland, Australia

Research Focus/Interests
  • Genetic engineering of mammalian cells to improve recombinant biologics production
  • Development of targeted genome editing techniques

 

Dr. Marianne Sheila Suriakumaran

PhD in Stem Cell Biology & Regenerative Medicine (2017), National University of Singapore

Research Focus/Interests
  • Vector design optimization and mammalian cell line engineering to efficiently produce high-titer antibody drugs for therapeutic use

 

Dr. Evan Tan

PhD in Molecular and Cell Biology (2017), National University of Singapore, Singapore

Research Focus/Interests
  • Recombinant adeno-associated virus (rAAV) production
  • Engineering of mammalian cells for rAAV production

 

Dr. Tran Bich Ngan Nguyen

PhD in Molecular and Cell Biology (2017), National University of Singapore, Singapore

Research Focus/Interests
  • Cell engineering for production of recombinant protein/ glycoprotein in mammalian cells

Year 2018

    Tan Heng Liang, Charlene Yong, Tan Bao Zhu, Fong Wey Jia, Jayanthi Padmanabhan, Angela Chin, Vanessa Ding, Ally Lau, Zheng Lu, Bi Xuezhi, Yang Yuansheng, Andre Choo (2018) Conservation of oncofetal antigens on human embryonic stem cells enables discovery of monoclonal antibodies against cancer. Scientific Reports 8: 11608

    Dawn Sow Zong Leong, Brian Kah Hui Teo, Janice Gek Ling Tan, Hayati Kamari, Yuan Sheng Yang, Peiqing Zhang and Say Kong Ng (2018) Application of maltose as energy source in protein-free CHO-K1 culture to improve the production of recombinant monoclonal antibody. Scientific Reports 8(1): 4037

    Justin Bryan Goh and Ng Say Kong (2018) Impact of host cell line choice on glycan profile. Critical Reviews in Biotechnology (Published Online)

    Congqiang Zhang, Xixian Chen, Nic D. Lindley, Heng-Phon Too (2018) A "plug-n-play" modular metabolic system for the production of apocarotenoids. Biotechnology and Bioengineering 115(1): 174-183

Year 2017

    Shu Hui Neo, Ka Yan Chung, Jia Min Quek & Heng-Phon Too (2017) Trehalose significantly enhances the recovery of serum and serum exosomal miRNA from a paperbased matrix. Scientific Reports 7(1): 16686

    Congqiang Zhang, Xixian Chen, Nic D. Lindley, Heng-Phon Too (2018) A "plug-n-play" modular metabolic system for the production of apocarotenoids. Biotechnology and Bioengineering 115(1): 174-183

    Woei-Yuh Saw, Erwin Tantoso, Husna Begum, Lihan Zhou, Ruiyang Zou, Cheng He, Sze Ling Chan, Linda Wei-Lin Tan, Lai-Ping Wong, Wenting Xu, Don Kyin Nwe Moong, Yenly Lim, Bowen Li, Nisha Esakimuthu Pillai, Trevor A. Peterson, Tomasz Bielawny, Peter J. Meikle, Piyushkumar A. Mundra, Wei-Yen Lim, Ma Luo, Kee-Seng Chia, Rick Twee-Hee Ong, Liam R. Brunham, Chiea-Chuen Khor, Heng Phon Too, Richie Soong, Markus R. Wenk, Peter Little & Yik-Ying Teo (2017) Establishing multiple omics baselines for three Southeast Asian populations in the Singapore Integrative Omics Study. Nature Communications 8(1): 653

    Jessna H.M. Yeo, Steven C.L. Ho, Susanto Woen, Mariati, Esther Koh, Tay Shi Jie, Peiqing Zhang, Yuansheng Yang (2017) Optimized selection marker and CHO host cell combinations for generating high monoclonal producing cell lines. Biotechnology Journal (Published Online)

    Jian'er Lin, Shu Hui Neo, Steven C. L. Ho, Jessna H. M. Yeo, Tianhua Wang, Wei Zhang, Xuezhi Bi, Sheng-Hao Chao and Yuansheng Yang (2017) Impact of Signal Peptides on Furin-2A Mediated Monoclonal Antibody Secretion in CHO Cells. Biotechnology Journal 12: 9

    Benjamin P.C. Soo, Julian Tay, Shirelle Ng, Steven C.L. Ho, Yuansheng Yang, and Sheng-Hao Chao (2017) Correlation between expression of recombinant proteins and abundance of H3K4Me3 on the enhancer of human cytomegalovirus major immediate-early promoter. Molecular Biotechnology 59(8): 315-322

    Faraaz Noor Khan Yusufi, Meiyappan Lakshmanan, Ying Swan Ho, Bernard Liat Wen Loo, Pramila Ariyaratne, Yuansheng Yang, Say Kong Ng, Tessa Rui Min Tan, Hock Chuan Yeo, Hsueh Lee Lim, Sze Wai Ng, Ai Ping Hiu, Chung Ping Chow, Corrine Wan, Chen Shuwen, Gavin Teo, Gao Song, Ju Xin Chin, Xiaoan Ruan, Ken Wing Kin Sung, Wei-Shou Hu, Miranda Gek Sim Yap, Muriel Bardor, Niranjan Nagarajan and Dong-Yup Lee (2017) Mammalian systems biotechnology reveals global cellular adaptations in a recombinant CHO cell line. Cell Systems 4(5): 530-542.e6

    Yoon Khei Ho, Li Han Zhou, Kam C. Tam, Heng Phon Too (2017) Enhanced non-viral gene delivery by coordinated endosomal release and inhibition of β-tubulin deactylase. Nucleic Acids Research (Published Online)

    Dawn Sow Zong Leong, Janice Gek Ling Tan, Christine Lin Chin, Shi Ya Mak, Ying Swan Ho and Say Kong Ng (2017) Evaluation and use of disaccharides as energy source in protein-free mammalian cell cultures. Scientific Reports Scientific Reports 7: 45216

Year 2016

    Quan Chen, Phyllicia Toh, Aina Hoi, Mo Xian, Xinying Peng, Yuansheng Yang, Haibo Zhang, Rui Nian, and Wei Zhang (2016) Improved protein-A chromatography for monoclonal antibody purification. Chinese Journal of Biotechnology 32(6): 1−12

    Steven C. L. Ho, Esther Y. C. Koh, Benjamin P. C. Soo, Mariati, Sheng-Hao Chao and Yuansheng Yang (2016) Evaluating the use of a CpG free promoter for long-term recombinant protein expression stability in Chinese hamster ovary cells. BMC Biotechnology 16: 71

    Steven C.L. Ho, Rui Nian, Susanto Woen, Jake Chng, Peiqing Zhang and Yuansheng Yang (2016) Impact of hydrolysates on monoclonal antibody productivity, purification and quality in Chinese hamster ovary cells. Journal of Bioscience and Bioengineering 122(4): 499–506

    Tessa Rui Min Tan, Kong Meng Hoi, Peiqing Zhang, Say Kong Ng (2016) Characterization of a Polyethylene Glycol-Amphotericin B Conjugate Loaded with Free AMB for Improved Antifungal Efficacy. PLoS One 11(3): e0152112

Year 2015

    Kah Fai Chan, Wahyu Shahreel, Corrine Wan, Gavin Teo, Noor Hayati, Shi Jie Tay, Wen Han Tong, Yuansheng Yang, Pauline M. Rudd, Peiqing Zhang and Zhiwei Song (2015) Inactivation of GDP-fucose transporter gene (Slc35c1) in CHO cells by ZFNs, TALENs and CRISPR-Cas9 for production of fucose-free antibodies. Biotechnology Journal (Published Online)

    Steven C. L. Ho, Tianhua Wang, Zhiwei Song and Yuansheng Yang (2015) IgG aggregation mechanism for CHO cell lines expressing excess heavy chains and strategies to reduce the aggregates. Molecular Biotechnology 57(7): 625-634

    Janice G.L. Tan, Yih Yean Lee, Tianhua Wang, Miranda G. S. Yap, Tin Wee Tan and Say Kong Ng (2015) Heat shock protein 27 overexpression in CHO cells delays activation of caspases to improve recombinant monoclonal antibody titer. Biotechnology Journal 10(5): 790-800

    Gajendra P. Singh, Shireen Goh, Michelangelo Canzoneri and Rajeev J. Ram (2015) Raman spectroscopy of complex defined media: biopharmaceutical applications. Journal of Raman Spectroscopy 46: 545–550

    Christine Lin Chin, Hing Kah Chin, Cara Sze Hui Chin, Ethan Tingfeng Lai and Say Kong Ng (2015) Engineering selection stringency on expression vector for the production of recombinant human alpha-1-antitrypsin using Chinese Hamster Ovary Cells. BMC Biotechnology 15: 44

    Ryan Haryadi, Steven Ho, Yee Jiun Kok, Helen X. Pu, Lu Zheng, Natasha A. Pereira, Bin Li, Xuezhi Bi, Lin-Tang Goh, Yuansheng Yang, Zhiwei Song (2015) Optimization of Heavy Chain and Light Chain Signal Peptides for High Level Expression of Therapeutic Antibodies in CHO Cells. Public Library of Science (PLOS) 10(2): e0116878

    Jake Chng, Tianhua Wang, Rui Nian, Ally Lau, Kong Meng Hoi, Steven C.L. Ho, Peter Gagnon, Xuezhi Bi, Yuansheng Yang (2015) Cleavage efficient 2A peptides for high level monoclonal antibody expression in CHO cells. mAbs 7(2): 403-412

Year 2014

    Mariati, Esther Y.C Koh, Jessna H.M. Yeo, Steven C.L. Ho, Yuansheng Yang (2014) Toward stable gene expression in CHO cells: Preventing Promoter Silencing with Core CpG Island Elements. Bioengineered 5(5): 340-345

    Wan Ping Loh, Bernard Loo, Lihan Zhou, Peiqing Zhang, Dong-Yup Lee, Yuansheng Yang and Kong Peng Lam (2014) Overexpression of microRNAs enhances recombinant protein production in Chinese hamster ovary cells. Biotechnology Journal 9(9): 1140-1151

    Steven C. L. Ho, Mariati, Jessna H. M. Yeo, Shiyi Goh Fang, and Yuansheng Yang (2014) Impact of Using Different Promoters and Matrix Attachment Regions on Recombinant Protein Expression Level and Stability in Stably Transfected CHO Cells. Molecular Biotechnology 57(2): 138-144

    Pete Gagnon, Rui Nian, Lihan Tan, Jason Cheong, Veronica Yeo, Yuansheng Yang, and Hui Theng Gan (2014) Chromatin-Mediated Depression of Fractionation Performance on Electronegative Multimodal Chromatography Media, its Prevention, and Ramifications for Purification of Immunoglobulin G. Journal of Chromatography A 1374: 145–155

    Susana Soo-Yeon Kim, Koon-Guan Lee, Ching-Siang Chin, Say-Kong Ng, Natasha Ann Pereira, Shengli Xu, and Kong-Peng Lam (2014) DOK3 is required for IFN-β production by enabling TRAF3/TBK1 complex formation and IRF3 activation. Journal of Immunology 193(2): 840-848

    Steven C. L. Ho and Yuansheng Yang (2014) Identifying and engineering promoters for high level and sustainable therapeutic recombinant protein production in cultured mammalian cells. Biotechnology Letters 36: 1569-1579

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