Eyeing up a new therapy

February 22, 2002

Gene therapy, the holy grail of the post-genome era, aims to render drugs and surgery unnecessary, altering the faulty genes in patients' cells by adding replacement strands of DNA. So finding the most efficient way of introducing the genes is crucial.

David Dean, associate professor in the division of pulmonary and critical care medicine at Northwestern University, Chicago, has been working on non-viral gene transfer into the cornea, the transparent coat of the eyeball that covers the iris and pupil and lets light into the eye.

Although much gene-therapy research is directed towards life-threatening diseases, Professor Dean added: "Vision loss is devastating and anything we can do to prevent it is important. And from a practical standpoint, the eye is accessible and can be manipulated without surgery."

Viruses are widely used to introduce genes. But they trigger significant immune responses and inflammation. This means that therapy cannot be administered more than once as the body will have been immunised by the first dose. The inflammation can sometimes be fatal.

Professor Dean's team used electroporation, which temporarily makes the cell membrane permeable by applying an electric pulse. The team injected firefly genes, which produce light emitting enzymes, and jellyfish genes, which produce fluorescent protein, into mice corneas and applied eight short pulses. Six hours after treatment, they detected the genes. Expression levels were constant for three days, but even after seven days they were significant, proving the technique to be highly effective.

Professor Dean's team plans to transfer a gene that helps to reduce eye inflammation caused by herpes simplex by producing a protein known to protect the eye from destruction by the immune system.

Several forms of glaucoma, the second most important cause of non-remedial blindness in the developed world, and cataracts, the main cause of blindness worldwide, have genetic components.

The results were published in the Journal of Gene Medicine .

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