Swift gene-editing may help revolutionize disease treatment

For the first time, scientists have found a way to efficiently and precisely remove genes from white blood cells of the immune system and to insert beneficial replacements, all in far less time than it normally takes to edit genes.

If the technique can be replicated in other labs, experts said, it may open up profound new possibilities for treating an array of diseases, including cancer, infections like HIV and autoimmune conditions like lupus and rheumatoid arthritis.

The new work, published Wednesday in the journal Nature, “is a major advance,” said Dr. John Wherry, director of the Institute of Immunology at the University of Pennsylvania, who was not involved in the study.

But because the technique is so new, no patients have yet been treated with white blood cells engineered with it.

“The proof will be when this technology is used to develop a new therapeutic product,” cautioned Dr. Marcela Maus, director of cellular immunotherapy at Massachusetts General Hospital.

Fighting cancer, HIV

That test may not be far away. The researchers have already used the method in the laboratory to alter the abnormal immune cells of children with a rare genetic condition. They plan to return the altered cells to the children in an effort to cure them.

This type of treatment with engineered white cells, called immunotherapy, has been limited because of the difficulty of making viruses to carry the genetic material and the time needed to create them.

But researchers now say they have a found a way to use electrical fields to deliver both gene-editing tools and new genetic material into the cell. By speeding the process, in theory a treatment could be available to patients with almost any type of cancer.

“What takes months or even a year may now take a couple weeks using this new technology,” said Fred Ramsdell, vice president of research at the Parker Institute for Cancer Immunotherapy in San Francisco. “If you are a cancer patient, weeks versus months could make a huge difference.”

The technique may also hold great promise for treating HIV, Wherry said.

The HIV virus infects T-cells. If they can be engineered so that the virus cannot enter the T-cells, a person infected with HIV should not progress to AIDS. Those T-cells already infected would die, and the engineered cells would replace them.

Seeking FDA approval

Scientists usually introduced replacement genes into T-cells with a type of virus that was disarmed so that it would not cause disease and that can insert new genes into cells. But when these viruses insert the genes into a cell’s DNA, they do so haphazardly, sometimes destroying other genes.

“We needed something targeted, something fast and something efficient,” Marson said. “What if we could just paste in a piece of DNA and avoid the viruses altogether?”

The idea would be to slip a type of molecular scissors, known as Crispr, into cells that would slice open DNA wherever scientists wanted a new gene to go. That would avoid the problem of using a virus that inserts genes pretty much at random.

They would also add a piece of DNA containing the new gene to be added to the cells.

One way to do that would be to use an electrical field to make the cells permeable. It required a herculean effort by a graduate student, Theo Roth, to finally figure out the right molecular mixture of genes, gene-editing tools and electrical fields to modify Tcells without a virus.

“He tested thousands of conditions,” Marson said.

Already the scientists are talking to the Food and Drug Administration about using the new method to precisely attack solid tumors, as well as blood cancers.

“Our intent is to try to apply this as quickly as possible,” Ramsdell said.