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Recombinant DNA technology may enable oral, rather than injectable, delivery of protein drugs

o receptors on the intestinal epithelial cells and be transported across the GI tract to the blood stream," Shen says. "Humans naturally produce transferrin to move iron through the blood to the liver, spleen and bone marrow. It has been used to carry some protein-based drugs in a piggy-back fashion to their necessary site of action."

The next step, Shen explains, was isolating the genetic code for G-CSF, a protein factor that stimulates white blood cell production in the body. G-CSF is used to make Neupogen(r) and Neulasta(r) - injectable drugs that work to keep an individual's white blood cell count at normal levels during chemotherapy.

After that, the researchers needed to bring transferrin and G-CSF together, a process that is detailed in the PNAS paper. "Through recombinant DNA technology, we combined the genetic codes for both human transferrin and G-CSF to create a new recombinant DNA, which, when expressed in a cell, will produce a protein with half transferrin and half G-CSF," says Shen. "We refer to this method as recombinant fusion protein technology."

Recombinant DNA technology utilizes a series of procedures to join (recombine) segments of two or more different DNA molecules. When put into cell culture, a recombinant DNA molecule multiplies itself to form a colony of daughter cells that secretes the desired protein. These cells become "factories" for the production of the protein coded for by the inserted DNA.

As it turned out, this was the case as well for the transferrin/G-CSF combination.

"Our recombinant fusion protein was administered orally, and when tested in mice, increased the white blood cell count for three days, whereas the injectable agents only maintain effectiveness for one day," Shen says. "We have finally produced an orally-administered protein with a desirable therapeutic activity. This technique can be used to create orally-administered versions of other currently injectable protein drugs such a
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Source:Eurekalert


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