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HOW DAVID BERRY’S INVENTIONS WORK

dFGF2: Protein to Treat Stroke
This invention resulted from Berry’s thesis research into compounds called glycosaminoglycans, which are complex sugar polymers. The best-known of these molecules is the anticoagulant heparin. Heparin-like glycosaminoglycans, formally known as heparin/heparan sulfate-like glycosaminoglcyans (HSGAGs), are present on the surface of every cell in the body. HSGAGs have 48 building blocks – compared to DNA, which has four, and proteins, which have 20. They can interact with a number of important proteins because of the significantly higher number of possible HSGAG sequences.

Berry investigated the way heparin interacts with a particular type of fibroblast growth factor protein called FGF2, which is involved in the formation of new blood vessels. He discovered a way to optimize FGF2 to treat stroke.

For FGF2 to have an effect on cells, it needs to form a dimer, where two FGF2s come together. Heparin and other HSGAGs facilitate this dimerization process. The dimerized FGF2s form a complex with two cell surface receptors. This entire five-member complex is brought into the cells, leading to the cellular response.

The new protein Berry et al. created, called dFGF2 or dimerized FGF2, functions as the two FGF2 molecules brought together by heparin. It thereby serves as three components of the five-member signaling complex. This entirely eliminates the need for the heparin component. Cells therefore respond to dFGF2 at a lower dose than they do for FGF2. Cells can also respond more to dFGF2 than to FGF2.

The dFGF2 protein reduces the variability in obtaining a cellular response. For the treatment of stroke, dFGF2 has a stronger effect than FGF2 and can produce its effect at a lower dose, reducing the chance for side effects.

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Internalized Heparin for Cancer
Berry discovered another use for heparin as a treatment for cancer. He discovered that when heparin, which is negatively charged, binds to a biodegradable polymer called a poly(B-amino ester), it results in a positively charged complex, about 200 nm in diameter.

Cells have a tendency to take up positively charged substances of ~200 nm or less in diameter through a process called endocytosis. Cancer cells have a faster rate of endocytosis than most normal cells. As a result, the polymer-heparin conjugate is selectively taken up by the cancer cells and the heparin is delivered to them without affecting the other healthy cells. This eliminates the side-effects common in treatments such as chemotherapies, which attack both healthy and cancerous cells.

Certain varieties of the poly(B-amino ester) polymers are better for certain types of cancers, so they can be matched for maximum effectiveness.

Cancer Magnet
In addition to its use as an internal delivery mechanism for heparin, Berry developed a new procedure to use heparin externally, as well. His self-described “cancer Band-Aid®” is a surface coating made from various complex sugars, including heparin. Although different coatings can have different functions, two specific sugars can cause cancer cells to bind to the surface, where their growth is prevented and from which they do not metastasize. Berry envisions this device being used after a surgery, such as the type used to remove melanoma, to ensure any “leftover” cancer cells are extracted from the body.

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Biohydrogen
Hydrogen gas is currently produced on an industrial scale, primarily for petroleum refining, using two techniques: electrolysis and steam methane reforming. Two techniques have been developed to produce hydrogen biologically from bacteria. The two biological hydrogen processes reduce the pollution and costs associated with steam methane reforming.

The first biological technique uses water to convert carbon monoxide to carbon dioxide and hydrogen. This reaction is currently part of steam methane reforming and is known as the water-gas shift reaction. In the current technique, a high-temperature environment and certain metal catalysis, such as a zinc-oxide, are required. This reaction has been estimated to consume up to 15% of the total operating costs of steam methane reforming, or between $0.76 and $1.70 per gigajoule.

The replacement technique Berry helped develop involves engineering specific bacteria to readily consume carbon monoxide from their environment. These bacteria have an enzyme complex that can undergo the same reaction as occurs in steam methane reforming, and are limited only by how much carbon monoxide they can consume. Estimates for a “biological water-gas shift” suggest operating costs of only $0.52 per gigajoule, with low capital costs of only $0.14 per gigajoule per year.

The second technique uses several engineering steps to replace the entire steam methane reforming process. Ten times more efficient than the biological processes, it could greatly undercut the costs of steam methane reforming techniques used today.

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