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Marletta began looking for protein fragments that bound to oxygen, but not to nitric oxide. He started with the genetic sequence for the section of the globin proteins that binds to oxygen. He then used a computer program to scan through genome databases for similar sequences. This turned up a group of similar sequences in single-celled organisms. Marletta studied these protein sequences and found a group of them that bind to oxygen but not to nitric oxide. By altering the sequences slightly, Marletta found he was able to tailor how tightly the protein binds to oxygen. This level of control means Omniox can design a protein that releases oxygen only when the surrounding levels of the oxygen are very low—meaning the protein must travel all the way to the hypoxic part of the tumor before it releases the oxygen.

Cary, who was formerly a postdoctoral researcher in Marletta’s lab, cofounded Omniox in 2006 to develop a therapeutic oxygen-carrying agent. The company has raised a total of about $4 million from the NCI and the University of California’s Institute for Quantitative Biosciences. The company is currently housed in the university’s biotech startup incubator, the QB3 Garage.

Omniox has so far demonstrated that its proteins accumulate in tumors in living animals, and that the proteins increase the oxygen concentration there.

Studies of the proteins are now underway at the NCI. Cherukuri, who is not affiliated with Omniox, has developed a tracer for use with magnetic resonance imaging that allows him to make a high-resolution, 3-D map of tumor oxygen concentrations.

Cherukuri is using this method to study the effects of Omniox’s agents in mice with hypoxic tumors. “When you have a very hypoxic tumor, and you inject the animal with [the Omniox agent], the oxygenation increases,” he says. He is working with General Electric to develop a human-scale prototype of this imaging system.

The Omniox and NCI studies are aimed at figuring out which of the company’s proteins works best, when the proteins should be administered, and whether the treatment truly improves the effectiveness of radiation therapy. The studies will also look out for any dangerous immune responses to the foreign proteins. If the results are promising, the company hopes to begin tests in human patients in 2013.

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Credit: Murali Churukali/NCI

Tagged: Biomedicine, cancer, radiation, blood, protein, cancer biology, oxygen carriers

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