Dupree, who majored in biochemistry and hopes to become a genetic counselor, has sometimes imagined what life would be like if that small error were not there. A year ago, in December, he learned how a technology called CRISPR might make that possible. A scientist named Eric Olson had requested some of Dupree’s blood a few months earlier, and Dupree had agreed. Soon he was rolling through the lab on his TiLite wheelchair so Olson, a biologist at the University of Texas Southwestern Medical Center, could show him the results—and what some scientists now predict is the likeliest way to cure Duchenne.

Using CRISPR, which makes it possible to snip DNA open at a precisely chosen spot, a team at the hospital had modified his cells in a dish, cutting through the extra exon. When DNA is broken this way, a cell races to make a repair, but the natural repair process typically makes a small error. This causes the unwanted genetic instructions to become unintelligible. The editing process required only a single step and had taken three days. In an image taken with a microscope, his cells were clouded with green puffs of perfect dystrophin.

Debbie Dupree and her son, Benjamin, 24, who has Duchenne muscular dystrophy. Ben has volunteered cells for gene-editing experiments.

“I try to be realistic with my expectations,” says Dupree. “But that gave me a sense of ‘Wow, this is here.’”

The potential to precisely and easily “edit” any genome using CRISPR is changing the way we think about nature. The CRISPR technique is often likened to a “search and replace” function for DNA. To laboratory scientists, it might better be compared to the discovery of fire. Every day they publish an average of eight scientific articles describing new uses of the technology—or merely reflecting on its exponentially expanding possibilities, like designer babies engineered with desirable traits and mosquitoes with DNA programmed to make them go extinct.

Ben Dupree cooks at his home near Dallas. Muscular dystrophy has weakened his legs so that he cannot walk.

Among these possibilities, the chance to end the pain and suffering of people like Dupree is CRISPR’s most compelling, if still distant, promise. In early-stage lab experiments, academic scientists are showing that gene editing offers new ways to attack cancer, to knock out HIV and hepatitis infections, even to reverse blindness and deafness. Companies aren’t far behind. Three startups in the Boston area have already raised a combined $1 billion and partnered with some of the world’s biggest drug companies, like Bayer and Novartis. “None of us can anticipate where this technology will end up,” says Olson. “I’m operating under the premise that it will take us farther than we can imagine.”

Scientists know the gene errors responsible for around 5,000 inherited disorders, and sequencing labs discover some 300 more each year. Some are one-in-a-billion syndromes. Duchenne is at the other extreme; it is one of the most common inherited diseases, affecting 1 in 4,000 boys. Girls are affected rarely, and to a lesser degree.

“I try to be realistic ... But that gave me a sense of ‘Wow, this is here.’”

Gene editing could be a way to erase such diseases, with a one-time, permanent alteration of a person’s DNA. It’s a step beyond conventional gene therapy—the 30-year-old idea of inserting entire replacement genes into a person’s cells, usually using a virus. That approach is impractical for some diseases. The gene for dystrophin, for instance, is too large to fit inside a virus, as CRISPR’s DNA-snipping proteins can. And sometimes a faulty gene that’s doing harm needs to be silenced, so adding a new one won’t help. CRISPR’s ability to delete and swap out genetic letters makes a huge new range of treatments possible. Some doctors are now calling CRISPR “gene therapy 2.0.”

To be sure, even gene therapy 1.0 has yet to fully arrive. After 30 years of research, scientists are still learning how to use viruses to move genetic instructions into a living person’s cells. Only two gene-replacement treatments for inherited disease have ever been approved, both in Europe. But Olson says he is convinced CRISPR is the most plausible way to stop Du­chenne. Early this year, he showed he could repair mutations in mice with muscular dystrophy after sending viruses stuffed with CRISPR ingredients into their veins. “A mouse is not a boy, but we think we know exactly what needs to be done,” says Olson. If it works, he adds, “this is a cure, not a treatment.”

Eric Olson, an expert in genetic engineering at UT Southwestern, began using CRISPR three years ago to develop a treatment for muscular dystrophy.

Olson says the very first human test of a CRISPR therapy in a patient with Duchenne could begin in two years, in what would be a small, exploratory clinical trial involving just a few boys. Working with Jerry Mendell of Nationwide Children’s Hospital in Ohio, a center for gene-therapy studies, they expect to give the treatment to monkeys during the next 12 months, a prelude to human tests. The researchers will also be looking to see whether the CRISPR gene therapy has unexpected effects. Accidental edits are a particular concern.

Dupree, who is following events in the lab, says he’s not expecting much for himself. He knows the studies could take years, and since his mutation is unique, he’d need a therapy tailored just for him. “I am more excited about the implications scientifically than any treatment for me,” he says. But his mother, Debbie Dupree, says chat boards and Facebook pages where parents gather are already alight with questions. “There is a lot of talk. People want to know when it will be available,” she says.

Duchenne patients and their families won’t be the only ones anxiously asking that question. Countless others facing deadly cancers or HIV, as well as sickle-cell anemia and numerous other genetic diseases, could soon be watching the fate of those CRISPR-altered cells in Olson’s lab. Are they the beginning of a new era of medicine or merely one more promising research result that will never make it out of the lab? In particular, researchers will need to solve the next challenge: safely and effectively editing DNA in cells throughout a human body, thus turning CRISPR from an invaluable lab tool into a medical cure.

Deleting diseases

CRISPR evolved inside bacteria, over billion-year time scales, as a form of immunity against viruses. Bacteria collect and store short snippets of DNA from viruses that have invaded them, spacing the segments out through their own genome in a pattern called clustered regularly interspaced short palindromic repeats—the term that gives CRISPR its acronym. When reinfected with one of these viruses, bacteria can create copies of these genetic snippets, which zip up letter for letter with the new virus’s DNA—signaling to a specialized cutting enzyme that it should attach itself and close, pincer-like, onto the viral genome and sever it.

“The interest right now is incredible. Before, no one was interested. No one cared.”

By 2013, teams of scientists in Boston, Berkeley, and Seoul separately showed that this naturally occurring bacterial immune process could be simplified and repurposed to cut DNA in human cells. Though scientists had previously created gene-editing proteins, these were difficult to design and build compared with the solution bacteria had devised. “Instead of version 2 or version 3, it was version three trillion,” says Tom Barnes, chief scientist of the CRISPR startup Intellia Therapeutics in Cambridge, Massachusetts. “And it went from no labs working on it to everyone working on it.”

Intellia is one of a trio of startups that have set up shop around Boston and raised about $300 million each to create CRISPR treatments; the others are Editas Medicine and CRISPR Therapeutics. Barnes says CRISPR vastly simplifies gene editing because of the way the cutting works. Just as bacteria spot and slice the viral genetic material, CRISPR can zero in on specific stretches of human DNA. The only ingredients needed are an editing enzyme—one named Cas9 is used most often—and a short “guide,” or length of genetic letters, to tell it where to cut.

It seems simple, but using it to create human treatments is anything but. And there’s one hitch that’s often overlooked: “editing” is a bit of a misnomer. Scientists have mastered cutting into DNA, which gives them something akin to a “delete” key for genes, in addition to the “add” function offered by traditional gene therapy. But they can’t as easily rewrite genes letter for letter, an aspect of the technology still being developed. For now, that mostly limits them to situations where deleting genes—or parts of them—is useful. Duchenne is one of those. Another is sickle-cell disease, a condition that in the United States affects mostly African-Americans. Medical researchers have given it relatively little attention in the past, but there’s an obvious DNA cut that might solve it, meaning a potentially elegant cure. Now Mitchell Weiss, a hematologist who treats people with sickle-cell at St. Jude Children’s Research Hospital in Memphis, says every gene-­editing company is calling him. “The interest right now is incredible,” he says. “Before, no one was interested. No one cared. But they need a proof of principle, and this is a good one.”

In addition to finding the kind of genetic problem to which CRISPR offers a solution, companies need a way to get the CRISPR instructions into the body. Most are counting on viruses for that job, but Intellia’s strategy is to package CRISPR into fatty blobs that liver cells suck up, just as if they were cholesterol. This August, at the annual CRISPR meeting in Cold Spring Harbor, New York, researchers from the company showed that with a single dose, they could alter the genomes of at least half the cells in a mouse’s liver. If ­Intellia can successfully edit liver cells in a person, that may let the company treat a slew of previously unassailable metabolic conditions like a form of hereditary amyloidosis, in which painful plaques build up in the body.

What’s obvious is that it will be easier to get CRISPR to work in some parts of the body than others. The easiest task is probably deleting genes in blood cells, since these cells can be removed from a patient and then put back. Already, a Chinese drug company has opened a study to create supercharged immune cells to battle cancer, and scientists at the University of Pennsylvania have announced similar plans with the financial backing of the billionaire Internet entrepreneur Sean Parker.