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What is High-Throughput Expression and Production?

Biointron 2024-09-20 Read time: 5 mins

High-throughput (HTP) expression and production refer to techniques that enable the accelerated and parallel expression and purification of a large number of antibodies, thus making large-scale repetition attainable. HTP technology was first developed in the 1990s with automated DNA sequencers and human genome sequencing. This approach was successfully expanded into measuring DNA, RNA, proteins, lipids and metabolites, with its use in research across various fields including immunology, cancer, ecology, cell biology and systems biology.1

The HTP production of monoclonal antibodies is a vital component of an efficient mAb discovery process, as it allows for the generation and screening of large quantities (100–1000 molecules) of selection outputs. This approach improves panel diversity, increasing the likelihood of identifying a monoclonal antibody with ideal antigen binding, biological function, and molecular characteristics.2

HTP expression and production of antibodies are particularly useful in therapeutic research, which often requires the study of many potential antibody targets simultaneously. Its speed is also a key advantage, in cases like pandemics and the necessity to accelerate preclinical research. This also makes it valuable in industrial production, where testing antibody effectiveness requires large sample sizes, making high-throughput production a necessity. 

Key Applications in Antibody Therapeutics

One of the primary advantages of HTP technologies is the ability to rapidly scale the production and testing of antibody candidates, which is critical in early-stage research and during drug development. This approach allows for the simultaneous screening of numerous antibody variants, which is particularly useful in cases where target binding, affinity, or efficacy needs to be optimized. 

Therapeutic research often requires evaluating many potential antibody targets, and HTP methodologies help streamline this process by enabling faster data generation. This rapid pace is especially advantageous in cases of public health emergencies, such as pandemics. For instance, during the COVID-19 pandemic, the speed at which potential therapeutic antibodies could be identified and tested became crucial. HTP expression systems can allow researchers to evaluate large antibody libraries and narrow down candidates for further development, contributing to the accelerated pace of preclinical and clinical research. 

High-Throughput Production in Industrial Settings

The utility of HTP production extends beyond academic research to industrial-scale antibody manufacturing. In biopharmaceutical production, the ability to test large sample sizes quickly is critical for ensuring product efficacy and safety. HTP technologies make it feasible to produce large quantities of antibody samples in parallel, a necessity for high-volume testing in industrial settings. 

Automation can be a key component of HTP expression and production. Robotic systems may be employed to handle the large number of samples required for parallel processing. Automated liquid handling systems, for example, enable the rapid preparation of expression cultures, while automated purification systems facilitate the high-throughput purification of antibodies. 

One of the major benefits of automation is the ability to reduce human error and variability in the production process. Automated systems can perform repetitive tasks with high precision, ensuring consistent production quality across a large number of samples. This is particularly important when dealing with therapeutic antibodies, where batch-to-batch consistency is critical for ensuring the safety and efficacy of the final product. 

HTP Processes for Bispecifics

For bispecific antibodies (bsAbs), the desired molecular specifications are more complex than for typical monoclonal antibodies (mAbs). These complexities include relative binding valencies, affinities to two targets, and molecular geometries, all of which must be optimized for the desired biological activity.  

Screening in bsAb format early in the discovery process is advantageous, but requires high-throughput (HTP) methods for both bsAb production and screening assays. Without these capabilities, fewer parental mAbs can be explored, limiting the diversity of molecules tested. This can extend project timelines due to the need for multiple rounds of engineering and optimization. Challenges such as lower expression titers and more heterogeneous purity profiles compared to mAbs further complicate bsAb production. Over the past decade, several technologies have been developed to address these issues, including advancements in gene integration, cell culture systems, and protein engineering solutions. For an efficient and cost-effective HTP bsAb production process, minimal experimental steps and consumable requirements are essential.2

Bispecific HTP.jpg
DOI:10.1080/19420862.2024.2311992

References: 

  1. Jia Baolei and Jeon Che Ok, 2016. High-throughput recombinant protein expression in Escherichia coli: current status and future perspectives. Open Biol. 6160196160196. http://doi.org/10.1098/rsob.160196

  2. Fawcett, C., Tickle, J. R., & Coles, C. H. (2024). Facilitating high throughput bispecific antibody production and potential applications within biopharmaceutical discovery workflows. MAbs, 16(1). https://doi.org/10.1080/19420862.2024.2311992


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