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Thursday / December 3.
HomeminewsGene Therapy Delivery for Glaucoma Advances

Gene Therapy Delivery for Glaucoma Advances

Scientists at the University of Wisconsin– Madison have identified a new way to deliver replacement genes that could treat glaucoma.

Glaucoma, one of the most common blinding diseases, is caused by excess pressure inside the eye, usually due to a clog in the trabecular meshwork, which drains fluid from the eye.

“Most glaucoma can be treated with daily drug treatment,” says Paul Kaufman, Professor of Ophthalmology and Visual Sciences at the University of Wisconsin–Madison. “Replacement genes could, theoretically, restore normal fluid flow for years on end, without requiring daily self-administration of eye drops that is inconvenient and may have local or even systemic side effects.”

In a study published in the scientific journal Investigative Ophthalmology and Visual Science, Professor Kaufman and colleague Professor Curtis Brandt, showed an improved tactic for delivering new genes into the trabecular meshwork.

We wanted to know if temporarily blocking the proteasome could prevent the destruction of the gene delivery vector and enhance delivery

The colleagues have been testing a vector based on feline immunodeficiency virus (FIV) to deliver the genes. Like the related human immunodeficiency virus, FIV can insert genes into the host’s DNA. The eye’s innate defenses against FIV, however, interfered with the delivery.

Virus particles contain genes wrapped in a protein coat and then a lipid membrane. After the virus enters the cell and sheds its membrane, defensive molecules from the host can “drag the virus particle to the cell’s garbage disposal, called the proteasome, where it is degraded,” said Prof. Brandt. “We wanted to know if temporarily blocking the proteasome could prevent the destruction of the gene delivery vector and enhance delivery.”

In the current study, FIV virus carrying a marker protein was placed on cells of the trabecular meshwork, with or without a chemical that blocks proteasomes.

Prof. Brandt said that above a dosage threshold, the treatment roughly doubled the transfer of genes entering the target cells. The new genes also spread more uniformly across the meshwork tissue. They believe that delivering more copies of the gene should give a greater therapeutic effect, opening the meshwork drain and reducing pressure inside the eye.

The present study concerns the tools for transferring genes, not the genes themselves, Prof. Brandt says. But even before the current study, he says he and Prof. Kaufman “have already identified at least two genes that could unplug the drain”.

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