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On the other side of the country,
Mark Walters, a blood and bone marrow
transplant specialist at the University
of California, San Francisco, Benioff
Children’s Hospital in Oakland, is gear-
ing up for trials that will use CRISPR
to repair the defective gene that causes
sickle cell disease. “With CRISPR, once
you’ve made that type of correction, [that
cell] is 100 percent healthy,” says Walters.
Another team is tackling the same
disease using a type of hemoglobin, a
protein in red blood cells, that’s nor-
mally made only in fetuses and newborn
babies. Researchers found that some
adults continue to produce these pro-
teins throughout their lives, and when
those adults also have sickle cell disease,
their symptoms are mild. So the interna-
tional team used CRISPR to disable the
gene that interferes with production of
this hemoglobin, resuming its produc-
tion and protecting the adult patients
against sickle cell disease.
Several other CRISPR studies are in
the works to treat a range of inherited
disorders, including hemophilia and
SCID-X1 (also known as X-linked
severe combined immunodeficiency, the
so-called “bubble boy” disease in which
babies are born without a functioning
immune system).GENE THERAPY WITHOUT CRISPR
The past year also saw success in a hand-
ful of experiments on conventional
gene therapy. Instead of using CRISPR
to repair disease-causing genes, these
treatments use hollowed-out viruses to
ferry healthy versions of genes into cells.
Millions of these altered cells are released
into the bloodstream or bone marrow in
hopes that enough will land in the right
places. But because scientists can’t predict
where the circulating genes may end up,
this shotgun approach has had unin-
tended, sometimes fatal, consequences
— including, in an earlier study, inadver-
tently activating leukemia-causing genes
in patients treated for SCID-X1.But in 2019, researchers learned
that using a different type of virus —
one related to HIV — to transport the
genes may prevent these side effects.
In an April study, researchers at St.
Jude Children’s Research Hospital in
Memphis, Tennessee, and UCSF Benioff
Children’s Hospital in Oakland collected
bone marrow from eight new borns with
SCID-X1. They loaded corrective genes
into the disabled HIV-related virus,
which carried them into the patients’
bone marrow stem cells. The infants
also received low doses of busulfan, a
chemotherapy that gave the doctored
stem cells room to grow. “So far, we
haven’t seen anything worrisome,” says
Ewelina Mamcarz, a pediatric oncologist
at St. Jude who led the research team.
The study recently added
its 12th patient.
“Gene therapy does
have its momentum
[back],” says Mamcarz,
reflecting on the field’s
setback after the earlier
study’s leukemia side
effects. “There’s so much
that still needs to be done,
and so many questions,”
she says. “[But] this is
how medicine evolves. We
always want to be better
than we were a week ago.”
In the future, the hope is that gene
therapy technologies will move beyond
mending simple genetic mistakes and
be used to combat big killers like dia-
betes or heart disease. “[Those diseases
are] more challenging, but a lot of them
would benefit from knocking out a bad
gene,” says Dunbar.
For now, though, researchers are opti-
mistic about the progress that’s already
been made. “All of this has been very
encouraging,” says Dunbar. “[And] for
sickle cell in the U.S. and hemophilia in
the developed world, these diseases may
soon be solved.”Turn the page to read about competition
for CRISPR: a new gene-editing tool.Early clinical trials brought promising results in- At St. Jude Children’s Research Hospital,
a gene therapy trial cured Gael Jesus Pino Alva
(pictured with his mother, Giannina) of SCID-X1,
the “bubble boy” disease.
Gene therapy clinical trials are underway at
places like UCSF Benioff Children’s Hospital
in Oakland.