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New cell-free glycosylation method accelerates development of protein therapeutics

Updated: May 10

The GlycoPRIME method could lead to faster development of therapeutics and a new, modular way to make medicines on demand in resource-limited settings

Glycosylation is important in the development of protein medicines, which include everything from anti-cancer drugs like Herceptin to flu and tetanus vaccines. Sugar structures allow these proteins to remain stable while enabling them to perform tasks, like attack a cancer cell or retrain the immune system. Developing these medicines has generally required many years and a laboratory with highly specialized equipment to grow mammalian cells. These mammalian cells naturally produce glycosylated proteins, but are slow-growing and can be difficult to engineer, limiting the number and diversity of glycosylation structures that can be built and tested.


To address this challenge, Weston Kightlinger and his Northwestern colleagues teamed up with us to develop a new approach called GlycoPRIME to build, test, and assess sets of enzymes that can modularly build sugars for protein therapeutics. The process involves producing and then mixing and matching enzymes in test tubes to discover and understand which enzymes are needed to build desired sugar structures. We used this process to develop a protein vaccine candidate modified with a sugar structure that could trigger the immune system, as well as a therapeutic antibody fragment with a sugar that can stabilize proteins as they circulate in the body. The results were published in the journal Nature Communications.


Future work will use other pathways developed in this paper to create glycosylated protein vaccines and therapeutics that can target certain areas within the body. The system could also be used to provide modular, on-demand biomanufacturing platforms that provide medicines or vaccines in resource-limited settings.


To learn more, see the press releases:

https://www.eurekalert.org/pub_releases/2019-11/nu-nma112719.php

https://phys.org/news/2019-11-method-protein-therapeutics.html

https://www.technologynetworks.com/drug-discovery/news/glycoprime-accelerating-protein-therapeutic-development-327751

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Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University

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