Optimization of a transient antibody expression platform towards high titer and efficiency

Area of Science:

• Biotechnology
• Molecular Biology
• Cell Biology

Background:

• Transient gene expression (TGE) is crucial for producing antibodies and recombinant proteins in mammalian cells.
• Chinese Hamster Ovary (CHO) cells are preferred for TGE due to their post-translational modification capabilities, high-density culture adaptation, and suitability for serum-free media.

Purpose of the Study:

• To optimize parameters for efficient TGE of antibodies from CHO cells.
• To develop an optimized TGE platform for early drug discovery, focusing on screening and production of therapeutic monoclonal antibodies (mAbs).

Main Methods:

• A matrix evaluation of factors including inoculum, transfection conditions, DNA quantity and type, and post-transfection culture conditions was performed.
• Investigated the impact of coding DNA amount and transfection complex kinetics/size on in vitro transfection efficiency.
• Introduced Filler DNA into the TGE process.

Main Results:

• Achieved an optimized TGE process with higher antibody titers, reduced costs, and decreased timelines.
• Demonstrated increased overall efficiency for early antibody material supply.
• Showcased the first report of an optimized TGE platform utilizing Filler DNA for therapeutic mAb screening and production in early drug discovery.

Conclusions:

• The optimized TGE platform significantly improves the efficiency of early antibody material supply.
• The use of Filler DNA in TGE offers a novel approach for therapeutic mAb discovery and production.
• This optimized process enhances the speed and cost-effectiveness of antibody development.