Researchers from Technical University of Denmark have produced CHO or mammalian cell lines which can produce 1, 2 g/L recombinant Alpha-1-antitrypsin protein. This breakthrough research can lead to better treatment of Alpha-, a genetic disorder.
Liver produces the protein Alpha-1-antitrypsin. After being secreted by the liver into the bloodstream, the protein circulates the whole body and protects lungs. However a genetic aberration in some people causes inability to produce this protein as a result they can suffer from shortness of breath, liver diseases and decreased lung function.
The disorder is being treated in various countries including the United States by using human plasma containing Alpha-1-antitrypsin. Approximately four grams of protein are infused into the patient per week as part of the treatment. The dose is also extremely expensive as it requires blood donation 900 donors and costs nearly 100,000 dollars a year to the patient.
A group of scientist from Novo Nordisk Foundation Center for Biosustainability at DTU has found a method to produce Alpha-1-antitrypsin protein in mammalian cells. The director of CHO cell line development at NNFCB at DTU, Bjorn Voldborg said that the current method of treating the genetic disorder involves infusion of blood from large number of donors. But with the recombinant alternative, the protein can be formulated, concentrated and purified without the need to depend on blood donors. This can ensure the security of supply for patients with this critical condition.
The researchers found a method to produce Alpha-1-antitrypsin in CHO cells which is the preferred cell line for producing human therapeutic proteins. The CHO counterpart normally is quite different from human counterpart as the latter has a very specific sugar structure while the former exhibits a variety of sugars making the protein ineffective in the human body.
The researchers introduced a human gene which decorated the desired human moieties on the sugar backbones of Alpha-1-antitrypsin protein. CRISPR-Cas9 was used to remove a number of undesired natural glycosylation genes of CHO cells.
This unique method resulted in production of a cell line capable of producing 1.2 grams per liter of cultured CHO cells. The method makes the production of Alpha-1-antitrypsin from CHO cells a feasible option which can potentially eliminate the need for human donors in the future.
Several pharmaceutical companies have shown interest in the commercial adaptation of the research. The research was published in the journal Metabolic Engineering.