The gene-editing tool is being tested in humans and the first treatment could be approved as early as this year.
Forget He Jiankui, the Chinese scientist who created gene-altered children. Instead, when you think of gene editing, you should think of Victoria Grey, an African-American woman who says she’s cured of the symptoms of sickle cell anemia. This week in London, scientists are gathering for the Third International Human Genome Editing Summit. It’s a big event in the field of gene editing, with researchers scaring the audience with their new ability to modify DNA, and ethicists starting to worry about what it all means. The event kicked off Monday with an eye on what organizers called China’s “misuse” of technology to create artificially modified babies known as “designer babies” in 2018. This was certainly an ethical tinderbox fire and raised deep questions about whether we should interfere with evolution, writes MIT Technology Review.
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But the debate about the designer child detracts from the real story of how gene editing is changing people’s lives through treatments applied to adults with serious illnesses.
In fact, there are currently more than 50 pilot studies using gene editing in human volunteers to treat everything from cancer to HIV to blood diseases, according to estimates provided by Harvard University gene-editing expert David Liu. Most of these studies – about 40 of them – are related to CRISPR, the most versatile gene editing technique that was developed just 10 years ago.
This is where Gray comes in. She was one of the first patients to be treated with the CRISPR procedure in 2019, and when she addressed a group in London, her story left the room in tears.
“Today I’m standing here before you to prove that miracles still happen,” Gray said of her battle with a disease in which deformed blood cells that don’t carry enough oxygen can cause severe pain and anemia.
But Gray’s case also shows the hurdles facing the first generation of CRISPR treatments, sometimes referred to as “CRISPR 1.0.” They will be very expensive and difficult to implement, and can be quickly replaced by a new generation of improved editing preparations.
The company behind Gray’s treatment says it has treated more than 75 people in its research on sickle cell anemia and its related disease, beta-thalassemia, and that the therapy could be approved for commercial use in the US within a year. This is expected to be the first CRISPR treatment to be marketed. The company hasn’t said how much it could cost, but you can expect the price to be in the millions.
The researchers say the advancement of this technique to medical use has been remarkably fast. “I think CRISPR has surpassed all previous genomic therapy technologies,” says Fedor Urnov, a researcher at the University of California, Berkeley.
For scientists, CRISPR is a discovery because of how it can cut the genome at certain places. It consists of a cutting protein paired with a short gene sequence that acts like a GPS navigator, moving to a predetermined location on a person’s chromosomes.
What’s more, this GPS sequence is very easy to change, says Jennifer Doudna, a Berkeley biochemist who won the Nobel Prize for inventing the method. “CRISPR is a technology that allows you to change programmed DNA,” she reminded those gathered at the summit.
Along with the company that cured Grey, a number of other biotech companies hope to be able to use the technology to develop successful treatments. Many of them are testing Liu’s list. But not all of these trials will be successful.
In January, for example, a San Francisco biotech company was forced to halt its own trial of a gene-editing drug to treat sickle cell anemia after its first patient’s blood cell counts dropped dangerously. The problem was caused by the treatment itself. The company’s shares have since fallen by more than 90%, and now the company’s future is in question.
The trick to all these efforts is still to get CRISPR to where it needs to be in the body. It is not simple. In Gray’s case, doctors removed the bone marrow cells and edited them in the lab. But before they were returned to her body, she underwent harsh chemotherapy to kill the remaining bone marrow and make room for new cells.
Essentially, a treatment similar to Gray’s treatment requires a bone marrow transplant. This is a test in itself, and not every patient will be ready for it. The company that treated the girl believes that the treatment is suitable for “severe” cases. The market, she estimates, includes 32,000 people in Europe and the US.
Even so, patients will not receive treatment if insurers and governments refuse to pay. This is a real risk. For example, another gene therapy for beta thalassemia was pulled from the European market after local governments refused to pay the $1.8 million price tag.
First-generation CRISPR treatments have other limitations as well. Most use this tool to damage DNA, essentially turning off genes, a process known as “genomic vandalism” by Harvard biologist George Church.
Among the treatments that try to break down genes is one designed to kill HIV. The other is the one Gray got. By breaking a specific piece of DNA, her treatment unlocks a second version of the hemoglobin gene, which people normally only use during infancy. Since hemoglobin is the erroneous sickle cell protein, the problem is solved by downloading another copy. According to Liu’s analysis, two-thirds of the current research is aimed at “destroying” genes in this way.
Liu’s lab is working on next-generation gene-editing approaches. These tools also use the CRISPR protein, but it is not designed to cut the DNA helix, but instead cleverly replaces individual genetic letters or makes larger changes. These are known as “base editors”.
According to Lewis Montoliu, a genetic scientist at Spain’s National Center for Biotechnology, these new versions of CRISPR have “less risk and better performance,” although getting them “to the right target cell in the body” remains challenging.
In his lab, Montoliu uses basic editors to treat mice for albinism, in some cases from birth. According to him, this is a step towards treatment that newborns could receive, but without changing the color of their skin. Instead, he dreams of putting Liu’s molecules in their eyes to correct the severe vision problems that albinism can cause.
So far, however, the albinism project is not a commercial venture. And this points to one of the biggest limits to the impact of CRISPR now and for the foreseeable future. Nearly all current CRISPR trials target either cancer or sickle cell anemia, and several companies are pursuing the same concerns.
This means that thousands of other hereditary diseases that can be treated with CRISPR are being ignored, Urnov said. “This is almost entirely due to the fact that most of them are too rare to be commercially viable,” he says.
However, at the meeting in London, Urnov will present his ideas on how to test treatments for even extremely rare diseases, including some genetic conditions so unusual that they affect only one person. This is not a commercial opportunity, but because CRISPR can be programmed anywhere in the genome, it is scientifically possible. Now that gene editing has made its first strides, Urnov says there is “an urgent need to open the way to the clinic for everyone.”
Focus has previously written about the success of CRISPR technology. A new study shows that experimental gene-editing technology is still highly effective in treating genetic blood disorders, even after three years of testing.
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