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Exploradio brings you captivating stories about science worth discovering and examines powerful questions worth answering.

After Three Decades, Gene Therapy Comes of Age

Gene therapy was once viewed as a promising new way to treat many incurable diseases -- until a tragic death occurred during a clinical trial. It’s taken nearly two decades for the industry to recover, but now several Northeast Ohio researchers are once again developing DNA as medicine.

In this week’s Exploradio, WKSU’s Jeff St.Clair looks at the science and business of gene therapy.

We’re in the auditory lab at NEOMED with researcher Hui Li. He points to a computer image of colored dots lining a small section of a mouse’s inner ear.

“So you can see," says Li, "we got a pretty strong infection in a majority of the region of the cochlea.”

When gene therapy was first developed, the adeno virus was used as the vector to deliver DNA to the cell nucleus. But a tragic death during a clinical trial in 1999 showed that the risks of an allergic reaction to the virus potentially outweigh its utility.

Yes, he’s happy to see an infection. Strange as it may seem, Li and his collaborator Jianxin Bao are developing a virus that can infect the tiny hair cells that allow us to hear.

That's a good thing, says Li.

“So in the future we can use this virus to deliver a certain type of genes to modify hair-cell function.”

Li received an Ohio Third Frontier grant to develop a toolbox of viruses that can infect a range of targeted cell types, not to make them sick, but to cure them with a one-time shot of viral-delivered DNA.

It’s called gene therapy – using DNA as medicine.

The rise and fall of gene therapy
It’s a technique developed in the late 1980’s that held great promise for treating patients with diseases like cystic fibrosis, Parkinson’s or rare blood disorders that had no other viable options.

I'm able to call myself a gene therapist again. --Bob Moen

Researchers recruit a virus to do what viruses do best -- infect a cell with its DNA payload, like a rocket delivering supplies to the space station. But in gene therapy, that payload is engineered to repair whatever mutation was causing the disease.

Bob Moen in 1986 formed the first company in the world to test viral-gene therapy. He says investors poured money into the new technology until 1999, when tragedy struck another group working at the University of Pennsylvania.

An 18 year-old subject in a clinical trial had a severe allergic reaction to the viral agent and died. It had, "a very stifling effect,” says Moen.  

He says the industry went into a tail-spin.  

“In fact, for many years when I went out and talked about our technology," says Moen, "I was actually discouraged by various bankers and other consultants to not use the word that we were a gene-therapy company.”

Moen later decided to join a group in Cleveland that was developing a different approach to gene therapy.

Non-viral gene therapy
Using technology invented by the late Richard Hanson at Case Western Reserve University, Moen says Copernicus Therapeutics sidesteps the need for a virus to deliver the DNA.  

“The system that Copernicus has is very attractive because it feels more like a regular pharmaceutical than viral gene therapy,” says Moen.

When you think about diseases that have burdened us for decades, we have the real potential to fix things now. --Marc Penn

Copernicus uses what co-founder Mark Cooper calls DNA nanoparticles, a patented approach that wraps the therapeutic gene with amino acids, the building blocks of proteins.

“Many diseases are caused by DNA mutations," says Cooper, "so there are classes of diseases that we’re very interested in providing therapy" by replacing the mutant gene with a normal copy.

The DNA nanoparticle is invisible to the body’s immune system, so, unlike the viral approach, repeated doses don’t cause an allergic reaction.

Cooper is raising the roughly $20 million he says is needed to fund a clinical trial for treating cystic fibrosis. But he says it’s not easy, given gene-therapy’s reputation.

“Many venture capital groups did not distinguish between viral vectors and our non-viral technology.”

A new era for gene therapy
Another Cleveland company, Juventas, is developing similar non-viral gene therapy to treat heart disease by turning on the body’s own repair system.

Founder Marc Pennsays new gene-editing tools, along with safer DNA delivery systems, both viral and non-viral, are opening a new era for gene therapy.

“When you think about diseases that have burdened us for decades, we have the real potential to fix things now, not just replace, and that’s huge.”

There is currently no FDA approved gene therapy of any kind. But Copernicus CEO Bob Moen says the industry has emerged from under the cloud that had surrounded it.

“That’s why I’m able to call myself a gene therapist again,” says Moen.

He predicts in five to 10 years, a variety of gene-therapy tools will be tailored to treat a variety of diseases. And he predicts Cleveland companies will be among the first to get them to market.

Jeff St. Clair is the midday host for Ideastream Public Media.