Nature-inspired technology creates engineered antibodies to fight specific diseases

Mar 25, 2009 By Anne Ju
In nature, proteins such as the enzyme hydrogenase assemble into complexes that travel across a cell membrane by the twin-arginine translocation pathway. In the laboratory, Matt DeLisa and coworkers have rewired this pathway for antibody-antigen interactions in a method that uses the reporter enzyme beta-lactamase as a readout of the interaction.

(PhysOrg.com) -- When viruses and bacteria invade the body, the immune system generates protective proteins called antibodies that bind to and destroy the invading pathogens.

A new genetic-engineering technique invented by Cornell researcher Matthew could pave the way for creating and cataloging disease-specific in the lab. The technique could revolutionize antibody-based drugs for such illnesses as Alzheimer's and cancer.

The method, which involves the efficient "readout" of protein-to-protein interactions within cells, was reported in the March 10 issue (Vol. 106 No. 10) of Proceedings of the National Academy of Science and is co-authored by Dujduan Waraho, a former graduate student.

DeLisa, an assistant professor of chemical and biomolecular engineering, and his collaborators have long studied a mechanism, called the twin-arginine translocation pathway, in bacteria and plant cells that allows completely folded proteins to diffuse across tightly sealed lipid membranes and infiltrate other parts of the cell.

Only a protein carrying a so-called can get across the membrane. Sometimes, though, another with and latches onto the protein with the signal peptide, essentially going along for the ride -- in fact, this phenomenon is called hitchhiker transport.

Inspired by this natural process, the researchers have developed a technology that can screen for antibody-antigen matches by taking a fragment of an antibody and attaching a signal peptide to it. They then attached to the antigen a reporter -- in this case an enzyme, beta-lactamase -- which causes resistance to such antibiotics as . The genes encoding these engineered proteins were placed into E. coli cells, enabling these cells to express the genes and make the proteins.

If the cells became resistant to penicillin, the researchers knew the antibody was a match for the antigen, because the proteins must have interacted in order to pass through the membrane and into the part of the cell that contained the antibiotic. Otherwise, the beta-lactamase could not have spread and caused penicillin resistance.

This method allows scientists to quickly look at antibody-antigen interactions and to screen antibody "libraries" to identify matches for specific antigens. Armed with this information, scientists can then engineer and manufacture antibodies in the laboratory.

"You can put any antigen you want into our system, and for the most part, it allows you to find antibodies that recognize the antigen," DeLisa said.

DeLisa has worked with Cornell Center for Technology, Enterprise and Commercialization (CCTEC) to obtain a patent on the technique. Meanwhile, the Ithaca-based biotechnology company Vybion Inc. has negotiated an exclusive license with CCTEC to use the technology, which it is using for in-house drug development and other related projects.

Provided by Cornell University (news : web)

Explore further: Education, breastfeeding and gender affect the microbes on our bodies

add to favorites email to friend print save as pdf

Related Stories

Carbohydrate-based vaccine against cancer?

Aug 29, 2005

Couldn't we be immunized against cancer? This sounds like a dream, but is in fact a thoroughly realistic research goal. American researchers have now taken an important step forward in the development of a cancer vaccine. ...

Cancer-fighting antibodies

Dec 22, 2008

(PhysOrg.com) -- MIT engineers have found that antibodies do not need a particular sugar attachment long believed to be essential to their function, a discovery that could make producing therapeutic antibodies ...

New Device Shines Light on Disease-Causing Molecules

Jul 08, 2008

If a doctor could identify a single molecule indicating the presence of a disease before the disease has a chance to harm the patient, the practice of medicine and the health of patients would be greatly improved. That’s ...

Recommended for you

Leeches help save woman's ear after pit bull mauling

Apr 18, 2014

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

Apr 17, 2014

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments : 0

More news stories

Treating depression in Parkinson's patients

A group of scientists from the University of Kentucky College of Medicine and the Sanders-Brown Center on Aging has found interesting new information in a study on depression and neuropsychological function in Parkinson's ...

Impact glass stores biodata for millions of years

(Phys.org) —Bits of plant life encapsulated in molten glass by asteroid and comet impacts millions of years ago give geologists information about climate and life forms on the ancient Earth. Scientists ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.