The problem is that Dupree’s body doesn’t make dystrophin, a protein in muscle fibers that acts like a shock absorber.
Without it, your biceps, calf muscles, and diaphragm slowly
turn to a fatlike substance. You end up on a ventilator, and
then your heart stops. Dystrophin is manufactured by a gene
that is not only the largest in the human genome but the largest anywhere in nature. It consists of 79 components known
as exons, each an instruction for one ingredient of the protein.
Dupree’s problem, he told me, is a “pseudo” exon—it’s as if in
the middle of this epic recipe someone had added a mistaken
instruction that read, “Stop the cooking.” There are thousands
of ways a gene this size can go wrong, and Dupree’s mutation—
a single letter of DNA that reads ‘G’ instead of ‘T’—is unique,
so far as scientists know.
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
“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 expand-
ing possibilities, like designer babies engineered with desirable
traits and mosquitoes with DNA programmed to make them
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, aca-
demic 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 com-
mon inherited disorders, affecting 1 in 4,000 boys. Girls are
affected rarely, and to a lesser degree.
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 muta-
tions 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
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 Chil-
dren’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 unex-
pected effects. Accidental edits are a particular concern.