Special Delivery of DNA to Cells: Interesting Method

David M. Lynn and fellow engineers at UW Madison have developed an ultrathin film for DNA packaging and delivery, for use in gene therapy.

When placed in or near a body tissue, the films are designed to degrade and release the DNA. Large strands of DNA cannot normally penetrate cells, so Lynn constructs his films with special polymers designed to bundle the genes into small tight packages that cells can import. Once inside, the genes instruct the cells to make proteins.

Lynn and his colleagues create the films one layer at a time using a dip-coating method, dunking first in one solution, then another. The individual layers are so thin it would take roughly 10,000 of them to equal the thickness of a single sheet of paper.

....The researchers alternate layers of DNA with layers of a polymer that is stable when dry but that degrades when exposed to water. Because the polymers carry a positive electric charge that is attractive to DNA, each polymer layer also "primes" the surface to accept the next layer of DNA. While electrostatic forces between the layers keep the film stable in dry, room-temperature conditions, the polymers break down easily in a wet biological environment - like the inside of a patient's body.

Lynn's laboratory has engineered a whole toolbox of different polymers to fine-tune the DNA delivery properties of their films. Using the layering method, they can control the amount of DNA by adding more layers, or can even layer multiple ingredients in a specific order. Tweaking the polymer structure slightly can change how quickly the films erode and thus how long cells are exposed to the gene therapy.

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Given the past morbidity and mortality of using viral vectors for gene therapy, it is important to find safe and effective alternatives. Although this method lacks much of the gene insertion machinery naturally present in viruses, it represent a very safe beginning for an alternative approach.