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Revolutionizing Vaccine and Therapeutic Production with a Novel Glycoengineering Platform

A novel glycoengineering platform developed by Assistant Professor Chris Lok-To Sham and his team from the Yong Loo Lin School of Medicine at the National University of Singapore (NUS Medicine) holds the potential to transform the production of vaccines and therapeutics for combatting infectious diseases. Glycoengineering focuses on manipulating sugars to create beneficial carbohydrates, and this innovative platform simplifies the customization and production of sugar carbohydrates known as glycans, which play a crucial role in various therapeutic applications.

The Role of Glycosyltransferases (GTs) in Glycan Production

Central to the glycoengineering platform is the use of glycosyltransferases (GTs), enzymes responsible for adding sugars and controlling the structural diversity of glycans. Assistant Professor Chris Sham likens these enzymes to Lego bricks, explaining that the more types of Lego bricks available, the greater the variety of glycans that can be built. The team discovered that the capsular polysaccharide (CPS), a sugar layer that encapsulates many bacteria, possesses an incredible diversity, with enzymes that can be harnessed to construct customized glycans.

A Versatile Platform for Glycan Engineering

In collaboration with their team from the Infectious Diseases Translational Research Programme at NUS Medicine, Assistant Professor Chris Sham and his graduate student Su Tong utilized the diverse pathways of bacterial CPS and its malleability for developing this groundbreaking glycoengineering platform. The platform offers increased versatility in modifying GTs, facilitating the engineering of newly-customized glycans. Creating customized glycans, which are essential for various therapeutic applications, necessitates a platform capable of inserting, deleting, substituting, and generally modifying glycan linkages.

Unprecedented Flexibility in Customized Glycan Production

The team discovered that by relaxing the specificity of the precursor transporters, they could expand the range of residues entering the cytoplasm. This breakthrough enables the production of customized glycans with unparalleled flexibility. Traditional methods of glycan customization primarily rely on in-vitro approaches, making the process challenging and less efficient for vaccine and therapeutic production. The new glycoengineering platform overcomes these challenges by showcasing the ability to genetically manipulate and engineer novel glycans, thus advancing the field of glycoengineering.

Promising Achievements and Future Development

Assistant Professor Chris Sham’s team has already achieved significant milestones using the glycoengineering platform. They successfully synthesized clinically relevant glycans such as the Galili antigen, blood group antigens, and Lewis antigens. These glycans have the potential to improve outcomes in organ transplants and blood transfusions by addressing situations where antibody rejection occurs due to incompatible blood groups, leading to severe inflammation and cell death.

The future development of this glycoengineering platform holds promise in creating a broader range of glycans to address specific needs. Assistant Professor Chris Sham envisions expanding the platform’s applications to other bacterial species, in addition to mammalian glycans. This would enable the production of more useful carbohydrates for countering immunological paralysis and graft rejection, among other applications.

The paper, titled “Rewiring the pneumococcal capsule pathway for investigating glycosyltransferase specificity and genetic glycoengineering,” was published in Science Advances on September 6, 2023.

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