Microgel Polymer Beads Provide Gene Therapy Vehicle

Originally Published MDDI June 2003

R&D DIGEST

A method for transferring proteins into cells via tiny polymer beads could prove useful for carrying vaccines or bits of DNA for gene therapy. According to chemists at the University of California, Berkeley, and Lawrence Berkeley National Laboratory, these beads can be embedded with a protein, such as a vaccine antigen, and can be made large enough to attract the attention of the immune system's scavenger cells. The scavenger cells would then engulf them and try to digest them with acid. 

According to Jean M. Fréchet, PhD, a professor of chemistry, and Niren Murthy, PhD, postdoctoral fellow, they have designed a polymer bead that breaks apart in scavenger cell acid. Thousands of molecule-sized fragments then expand and burst the cell's digestive chamber before the acids can degrade the antigens. The researchers explain that the method overcomes limitations of similar techniques. With previous methods, the cell's digestive acids could destroy the protein antigens before they were displayed on the cell surface. Without such display, the immune system cannot detect the presence of the foreign protein. 

Fréchet is head of materials synthesis in the materials science division at Lawrence Berkeley National Laboratory and director of the organic and macromolecular facility at its molecular foundry. He says the microgel bead technique skirts the disadvantages of current injectable vaccines that employ deactivated viruses to transport antigens to the cell interior. Once there, the antigens can stimulate an immune attack against an invading organism or a cancer. He says the new method's main advantage is that it's simple. 

Microgel polymer beads were selected because they have been shown to be taken up by scavenger cells and degraded. Fréchet attempted to create a bead that would, under the right conditions, burst into so many pieces that osmotic pressure would draw water into the cell's digestive chamber quickly enough to rupture it before the useful proteins could be degraded. 

To create the beads, polymer chemicals are mixed with the protein antigens in a solvent, hexane. The polymer chemicals in the spheres solidify into beads with the protein embedded. Fréchet's technique can produce beads of varying sizes for specific applications. Diameters can range from about half a micron, which can be used for the immune system's macrophages, to about a tenth of a micron, to target other types of cells involved in the immune system. 

The researchers say tests conducted in cultured cells have been promising, and justify current tests involving mice. Animal experiments are needed to prove the method works in the body and does not have unsuspected side effects, Fréchet says. Nevertheless, he predicts that the method will have broad applications in delivering proteins, genes, or antisense RNA into cell interiors, complementing conventional techniques.

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