

OHSU researchers reach major gene therapy breakthrough

 – Contributing Reporter

Researchers at Oregon Health and Science University have made a major breakthrough that could vastly improve the targeting and efficiency of gene therapy.

They’ve discovered a protein common in most cells that can be used to transport genetic material from a cell’s outer wall to its interior, creating a pathway where treatment methods could hitch a ride without destroying the cell.

“It’s the doorway to the cell, if you like,” said Michael Chapman, an OHSU biology professor and researcher who worked on the discovery. “The hope is to target these therapies only to diseased cells. And, having identified this protein, we can now start to understand how it interacts.”

Chapman and a team of researchers from OHSU and Stanford University released their findings today in the journal Nature.

In gene therapy, scientists use a virus to transport genetic material into cells for treatment.

If you think of the AAV virus as a tiny space shuttle that can be modified to take a cargo of genetic therapy treatment, then the protein is the space station loading dock that allows the virus and its cargo to attach and enter the cell without harming it.

Until now, researchers didn’t understand what that loading dock was or how to find it. So therapy methods could only take a very broad splatter approach, binding to an array of cells.

“That’s why some of the earliest gene therapy trials failed years ago. (Without specific targeting), the virus was inserted into a place where it ended up causing cancer,” Chapman said.

That splatter approach limits the types of diseases that gene therapy can treat. A few conditions, like inherited blindness and hemophilia B, don’t need specific targeting for treatment, Chapman said.

But there are a host of other diseases that could be treated with gene therapy once we better understand how to target them through the protein gateway, he said.

“These diseases (inherited blindness and hemophilia B) are low hanging fruit where you don’t need specific targeting to a place where you’re delivering treatment,” Chapman said. “As gene therapy gets more specific, we’ll need these new (discoveries) to complete the picture.”

Still, the discovery will likely improve delivery methods for the low-hanging-fruit diseases before we see treatments for some of the more difficult issues, he said.

“I think it will be a decade or more before we see big improvements from this,” Chapman said. “After all, the first gene therapies are only just getting clinical approvals.”

The next step for Chapman is to look at the protein gateway in more detail.

Proteins often get modified in the body as they interact with cells. And sometimes small arrays of sugar or phosphate will attach to the protein surface in specific patterns.

The hope is those patterns will be specific to damaged or diseased cells, which means the protein and its cargo could travel directly to only those cells, he said.

“What we’ve really done is removed a roadblock that’s been around for 20 years,” Chapman said. “That, in turn, should help the multitude of groups working on gene therapy make real progress. It’s really a fundamental step in the science.”

 – Contributing Reporter