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Cell Line Development

Empowering biologics production

In the Cell Line Development group, we focus on developing novel platform technologies for the rapid generation of Chinese Hamster Ovary (CHO) cell lines producing high titer and excellent quality therapeutic antibodies to meet the industrial needs. From cell transfection to clinical development, we engineer the cell lines to improve the efficacy of biologics development.


Our Capabilities

REDUCED TIME v6
HIGH TITER v4
STABLE CELL LINE v4

Our in-house developed technology enables rapid generation of high producing and good quality CHO production cell lines; generating high producing clones with titre up to 5g/L in fed-batch cultures within 9 weeks. The generated cell lines have stable production of more than 60 generations to ensure successful scale up for large scale manufacturing.


Performance of a biosimilar–producing CHO cell line generated using our multi-cistronic vector technology

Titre Graph
High Viable Cell Density

(Data collected in 14-day bioreactor fed-batch cultures)




Our Technologies

CHO Targeted Integration Platform v4

"SWAP and SWITCH" Targeted Integration Technology

  • Precision - control expression level of multiple genes
  • Simplicity - reduce the complicated process of screening many clones


  • Multi Cistronic Vectors for CLD v4

    Multi-cistronic vectors for CHO K1 cell line development

  • Accuracy - minimise non-expressing clones with the tight selection strategy
  • Enhancement - enhanced and optimised expression

  • Definition of multi-cistronic vectors: vectors that encode nucleotide sequence of IRES and 2A peptides, can simultaneously express two or more separate proteins from same mRNA

    Targeted integration technology utilises Recombinase-Mediated-Cassette-Exchange (RMCE), which recognises pre-determined active recombination sites in the genome and substitute the sequence with a new transgene. Multi-cistronic vector adopts Internal Ribosome Entry Site (IRES) elements to allow the expression of multiple genes in one transcript.



    OUR TRACK RECORD

    Industry Collaboration v4
    PROVEN CLINICAL RESEARCH v4
    HUB OF KNOWLEDGE v4

    Featured publications:

  • Multiplexed engineering glycosyltransferase genes in CHO cells via targeted integration for producing antibodies with diverse complex‑type N‑glycans (2021)
  • Optimized Selection Marker and CHO Host Cell Combinations for Generating High Monoclonal Antibody Producing Cell Lines (2017)
  • IRES-mediated tricistronic vectors for enhancing generation of high monoclonal antibody expressing CHO cell lines (2012)
  • Landmark patent & IP:

  • Promoters for high level expression (2020)
  • Mutated IRES for controlled gene expression (2017)
  • IRES mediated multi-cistronic vectors (2014)
  • Modified human CMV promoters that are resistant to gene silencing (2012)



  • The Team

    Yang Yuansheng

    Dr. Yang Yuansheng

    yang_yuansheng@bti.a-star.edu.sg
    Principal Scientist

    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
    Loh Han Ping

    Dr. Loh Han Ping

    loh_han_ping@bti.a-star.edu.sg
    Research Fellow

    PhD in Biological Sciences (2019), Nanyang Technological University, Singapore

    Research Focus/Interests

    • Cell line development for the production of heparan sulphate/ heparin in mammalian cells
    Dr Tran Bich Ngan Nguyen

    Dr. Tran Bich Ngan Nguyen

    nguyen_tran_bich_ngan@bti.a-star.edu.sg
    Research Scientist

    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