A U.S. patent was granted to Ohio University on Feb. 24 for “Growth hormone and interferon-alpha 2 glycoproteins produced in plants.”
Dr. Marcia Kieliszewski, Professor of Chemistry, is one of the inventors, along with Jianfeng Xu, John Kopchick, Shigeru Okada, and Gary Meyer.
Dr. Marcia Kieliszewski
Abstract: Methods of increasing the yield in plant expression of recombinant proteins comprising engineering glycosylation sites into cloned genes or cDNAs for proteins using codons that drive post-translational modifications in plants; and engineering the cloned genes or cDNAs to contain a plant secretory signal sequence that targets the gene products (protein) for secretion. The methods result in increased recombinant glycosylated protein yields. Proteins produced according to these methods are disclosed.
Summary of the Invention
The present invention provides novel methods of producing glycoproteins in plants. The glycoproteins include a glycosylation site element and a core protein element. In some embodiments, the core protein element can be of mammalian (including human) origin, and in some embodiments, the core protein element can be a biologically active protein. In some cases, the protein can be an FDA-approved recombinant protein that is used therapeutically, e.g. recombinant human growth hormone (“hGH”). The glycosylation site is an amino acid sequence that acts as a target for glycosylation by the plant.
One feature of the present method is an increase in yield in protein production. By including a glycosylation site(s) and a signal peptide sequence in the expressed protein, recombinant protein yield considerably increases in comparison to expression of the same protein in plants without the glycosylation site and signal peptide sequence.
Glycoproteins produced according to the method exhibit additional advantages over their wild-type counterparts, including increased solubility, increased resistance to proteolytic enzymes, and increased stability. Another important feature includes increased biological half-life as compared to wild-type proteins….
This invention was supported in part by NSF Grant No. MCB9874744 and USDA Project No. OHOW200206201.
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