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

Transferrin, a plasma protein found in blood, can be fused with large, protein-based drugs such as granulocyte colony-stimulating factor (G-CSF) to create a new oral compound that is capable of surviving the journey through the gastrointestinal (GI) tract and then able to cross over into the bloodstream to be used by the body, according to research from the University of Southern California School of Pharmacy.

This technology may allow for oral administration of drugs that previously could only be given by injection, notes Wei-Chiang Shen, Ph.D., professor and acting chair of the Department of Pharmaceutical Sciences. Shen, along with colleagues David Ann, Ph.D., professor of molecular pharmacology and toxicology, and Yun Bai, doctoral student in the Department of Pharmaceutical Sciences, wrote a paper on this research that will appear in the May 17 issue of the Proceedings of the National Academy of Sciences (PNAS), which is currently available online.

"Many of today's oral medications are made from small molecules, like amino acids or lipids, and their permeability allows them to be absorbed from the intestine into the body," says Shen. "On the other hand, protein-based drugs are large and bulky, which can prevent them from crossing the intestine and gaining access to the sites where they are needed. They are also very sensitive to digestive enzymes and may be destroyed by stomach acid before they can be absorbed." To sidestep the difficulty of getting these large protein drugs through the GI tract intact, pharmaceutical scientists have looked at other ways to deliver protein-based drugs-such as via needle-free injections or through inhalation. But, these delivery methods pose their own significant challenges. Ultimately, Shen and colleagues began to reconsider the possibilities of oral drug administration.

Their first breakthrough came when they began to recognize the potential uses of transferrin. "We discovered that transferrin can bind t 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 s insulin, growth hormone, and erythropoietin, a medication to increase red blood cell counts."

Recombinant DNA technology has and will enable the pharmaceutical industry to produce safer, more pure and more effective versions of therapeutic proteins, Shen adds.

"Since recombinant therapeutics utilize human proteins, they do not induce an unwanted immune response like products created from non-human sources often do."

On behalf of Shen and his collaborators, USC holds the patent to the new recombinant fusion protein technology. The research was supported by grants from the National Institutes of Health.



Related biology news :

1. Live Recombinant Adenovirus Vaccine Technique Explored
2. Novel technology detects human DNA mutations
3. Novel antiviral technology inhibits RSV infection in mice
4. The BIOS Initiative - open source biotechnology is born
5. Revolutionary nanotechnology illuminates brain cells at work
6. Study: homemade gene expression technology unreliable
7. First technology to remove prions that cause vCJD from blood launched
8. Integration of Agilents MS technology, Proteome Systems software to help scientists in proteomics research
9. Agilent Technologies new genome analysis technology set to accelerate Australia fight against mesothelioma
10. First production of human monoclonal antibodies in chicken eggs published in Nature Biotechnology
11. Vietnam war technology could aid elephant conservation
Post Your Comments:

(Date:4/14/2016)... 2016 BioCatch ™, the ... announced the appointment of Eyal Goldwerger as ... Goldwerger,s leadership appointment comes at a time of ... deployment of its platform at several of the world,s ... discerns unique cognitive and physiological factors, is a winner ...
(Date:3/31/2016)... , March 31, 2016   ... ("LegacyXChange" or the "Company") LegacyXChange is excited ... of its soon to be launched online site for ... ) will also provide potential shareholders a ... DNA technology to an industry that is notorious for ...
(Date:3/29/2016)... , March 29, 2016 ... "Company") LegacyXChange "LEGX" and SelectaDNA/CSI Protect are pleased to ... ink used in a variety of writing instruments, ensuring ... of originally created collectibles from athletes on LegacyXChange will ... analysis of the DNA. Bill Bollander ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... Researchers at the Universita Politecnica ... in people with peritoneal or pleural mesothelioma. Their findings are the subject of a ... , Diagnostic biomarkers are signposts in the blood, lung fluid or tissue of ...
(Date:6/23/2016)... , June 23, 2016 A person commits ... the crime scene to track the criminal down. ... U.S. Food and Drug Administration (FDA) uses DNA evidence to ... Sound far-fetched? It,s not. The FDA has ... to support investigations of foodborne illnesses. Put as simply as ...
(Date:6/23/2016)... , June 23, 2016   EpiBiome , ... secured $1 million in debt financing from Silicon Valley ... up automation and to advance its drug development efforts, ... new facility. "SVB has been an incredible ... the services a traditional bank would provide," said Dr. ...
(Date:6/23/2016)...  Blueprint Bio, a company dedicated to identifying, protecting ... has closed its Series A funding round, according to ... "We have received a commitment from Forentis Fund that ... meet our current goals," stated Matthew Nunez . ... complete validation on the current projects in our pipeline, ...
Breaking Biology Technology: