Advancements in GS-CHO technology and their impact on the advancement of biopharmaceuticals
Lonza, a global leader in GS-CHO expression systems, is pushing the boundaries of biotherapeutic development and manufacturing. The company's latest innovation involves building an industry-leading assembly for its GS Xceed CHOK1SV GS-Kogenome, which incorporates 3D interactome datasets, epigenetic markers, and other genome-wide readouts to deepen the understanding of CHO cell factory regulation.
One of the key components in addressing the challenges faced by the biomanufacturing industry is optimising the expression vector DNA. Lonza is improving vector design through the development of novel promoters, enabling better control of product gene expression levels within the host line for improved titer and product quality.
High-throughput transient gene expression is used to quickly screen expression vector variants for the best titer. For larger quantities of therapeutic protein candidates, vector optimization work is performed on stable pools. Screening analysis considers factors like final product titer, product quality, assembly characteristics, and cell growth during a fed-batch process.
Screening analysis identifies the expression vector design that correlates with the highest producing stable pool, along with optimal product assembly. Lonza screens vector variants using CHO-based expression workflows, tailored to the therapeutic product's development stage and customer needs.
Titer optimization is crucial in the biologics industry to reduce the cost of goods while working with an increasingly wide range of therapeutic protein formats. For products with three constituent protein chains, gene copy number ratio can be changed to optimise expression. Lonza's GS piggyBac transposase technology can accommodate large DNA cargo and targets genetically stable parts of the host CHO cell genome, resulting in higher yields compared to conventional vector designs.
These advancements in expression vector design, including the use of novel engineered components, are needed to meet industry challenges head on. Data science tools, such as machine learning and AI, can potentially de-risk the entire protein expression workflow and facilitate precise predictions in biomanufacturing processes.
The GS Effex cell line, developed by Lonza, creates afucosylated antibodies at high titers due to targeted gene edits. These therapeutic proteins have shown success in treating autoimmune diseases, cancer, and recently, neurodegenerative diseases.
The biomanufacturing industry must build its manufacturing capacity and innovate upon existing platform technologies to meet the rising demands for broad and effective treatment offerings. Lonza offers drug developers the option to license its technology for use in their own lab or outsource their therapeutic protein development and manufacturing to Lonza at any stage in the process.
Meanwhile, other companies like GlycoExpress GmbH are also making strides in the field of GS-CHO expression platforms for the production of recombinant therapeutic proteins. The use of GS-CHO based expression systems, widely used for producing monoclonal antibodies and other recombinant therapeutic proteins, is expected to continue shaping the future of biotherapeutics.
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