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Nashville–based GenHunter Corporation has been granted a US patent (7,268,116) for a new protein expression technology.
Nashville–based GenHunter Corporation has been granted a US patent (7,268,116) for a new protein expression technology. The method, dubbed Trimer-Tag, allows soluble receptors or polypeptides to be produced as secreted proteins that self assemble with a trimeric tag to form a fusion protein that can target trimerized ligands such as TNF-a. The technology takes advantage of the C-prodomains (Trimer-Tag) of collagen proteins, which are capable of efficient self-trimerization and strengthened by disulfide bond linkages.
By offering a new platform for the creation of trimeric soluble receptors and antibodies, the Trimer-Tag technology improves the targeting of corresponding disease-causing homotrimeric ligands, such as the TNF family of cytokines and HIV gp120.
“For many years, biotech and pharmaceutical companies have been trying to find a way to make secreted proteins trimeric in order to target TNF-a (a major inflammatory cytokine),” says Peng Liang, PhD, founder and chairman of GenHunter. “GenHunter’s methodology creates a way to produce proteins that are homotrimeric, strengthened by disulfide bond linkages, and are not toxic to the body.”
The other main technology used to bind TNF-a and other cytokine targets is Fc-tags. Trimer-Tags are better because they allow a stronger bond to be formed, says Liang. The trimerized protein is created using a vector that contains DNA encoding for collagen, into which the cDNA sequence of the protein to be trimerized is inserted (the sTNF receptor in this example). Collagen, a homotrimeric rope structure, is the most abundant, naturally occurring protein secreted by mammals. By fusing the soluble TNF-a receptor to the Trimer-Tag, a trimeric TNF-a receptor is created which can then be used as a therapeutic protein. This homotrimeric receptor TNF blocker can then more effectively attach to its homotrimeric target, because the three receptor prongs grab on to the three ligand prongs, creating a bond that is stronger than the bonding between a dimeric Fc-tag and a trimeric target (see figure).