UB Biologists Clone, Express Key Iron-Binding Protein With Commercial Promise

BUFFALO, N.Y. -- A powerful human protein that destroys pathogens by depriving them of the iron they need to grow has been cloned, expressed and purified by University at Buffalo biologists, who have filed for patent protection on the research.

Recombinant lactoferrin has commercial potential for products ranging from an antimicrobial agent to an improved infant formula.

The research was funded by FerroDynamics, Inc., a biotechnology company in Houston that has licensed worldwide rights to recombinant human lactoferrin and its commercial uses from the University at Buffalo.

Found in most physiological fluids, such as tears, mucus and mother's milk, the protein's critical feature is its ability to bind iron, making much of it unavailable to invading pathogens.

"Lactoferrin's high affinity for iron makes it a key player in the human immune system," explained Darrell Doyle, Ph.D., professor of biological sciences at UB who directed the research.

"It's a natural antibiotic," he said.

But cloning the human gene for lactoferrin has not been easy.

"For years, people have tried unsuccessfully to clone a full-length lactoferrin gene," noted Marian L. Kruzel, Ph.D., president of FerroDynamics.

Cloning was difficult because of the large fragment of DNA that had to be expressed: The gene that codes for lactoferrin is about 2,000 base pairs long.

Identifying the right expression system for reproducing the protein also was critical.

Because the right kinds of sugars are necessary for the protein to function properly, common expression systems like bacteria, which do not glycosylate proteins (add sugars to them), cannot be used.

The UB team was successful when Paul Gollnick, Ph.D., assistant professor of biological sciences at UB, and Tomasz Kurecki, Ph.D., senior research support specialist, used the PCR (polymerase chain reaction) method to clone the full-length human lactoferrin gene.

Using a picha pastoris yeast expression system, FerroDynamics confirmed the ability to produce human lactoferrin on the laboratory scale.

Now in the process of scaling up from pilot production of lactoferrin, FerroDynamics expects to have its first product on the market within two years. The company's primary focus is the market for topical antimicrobial products.

At the first sign of infection, white blood cells release lactoferrin, which fights bacterial invaders by depriving them of the iron critical to their growth.

Unlike currently available antibiotics, each of which is designed to combat a specific type or group of bacteria, lactoferrin is nonspecific.

According to Kruzel, that provides an important advantage.

"Over time, bacteria being treated with antibiotics such as penicillin or streptomycin can evolve strains that are resistant to specific characteristics in those drugs," he explained.

But human lactoferrin binds to, or sequesters, the iron of all pathogens.

"Without iron, pathogens cannot survive," he said.

Among the other lactoferrin products FerroDynamics expects to market is an additive to make baby formula more like human milk.

Studies of breast-fed infants have shown that babies fed human milk, which is rich in lactoferrin, absorb iron from it much more efficiently than babies fed infant formulas fortified with iron, Doyle explained.

Other products that are now possible based on the UB research include food preservatives, dietary supplements and skin-care products.