Tracy Antonelli and her three daughters suffer from thalassemia, a blood disorder that saps their strength, leaves them anemic, and requires them to visit Boston Children’s Hospital every three weeks for transfusions. “We’re lucky we have a treatment regimen that’s available to us, but it’s cumbersome,” Antonelli says.
A technology in development at several drug companies offers some hope for a more effective and convenient treatment for the Antonellis, and patients with other serious genetic conditions, such as sickle cell anemia. The technique is called Crispr, which stands for clustered regularly interspaced short palindromic repeats. Crispr, a method for editing the human genome—the complete set of an individual’s genetic material present in any of her cells—allows scientists to cut out faulty sections of DNA that can lead to serious illnesses and replace them with healthy ones. In the two-part process, first an RNA “guide” molecule locates the part of the DNA that needs to be removed or fixed. Then a Cas9 protein attaches to the DNA and cuts out the mutation. In some cases, scientists can then insert a good strand of DNA. Scientists began using Crispr in human cells about two years ago.
“It’s completely revamped the way we think about genetic disorders and how to fix them,” says Eric Topol, director of the Scripps Translational Science Institute in La Jolla, Calif., a research center focused on precision medicine. Scientists say Crispr is cheap and easy to use compared with other genome editing techniques. It’s used by medical and biological researchers all over the world and has been cited in thousands of scholarly papers. The technology has become a magnet for venture capital, even though medical applications are several years away. Four companies developing Crispr-based therapies have raised more than $170 million combined.
Many of them, including Editas Medicine in Cambridge, Mass., have said they plan to use Crispr to treat diseases in children and adults. Editas scientists are using it in experiments on eye cells to try to eliminate a defective gene linked to Leber congenital amaurosis, a condition that causes blindness in children. The company, founded two years ago with $43 million from Polaris Partners, Third Rock Ventures, and Flagship Ventures, presented early test results to the American Society of Gene & Cell Therapy in early June. It may begin testing drugs in patients next year.
The expectations raised by Crispr have roused ethical questions about the technique and its potential uses. In March, MIT Technology Review reported that OvaScience, a biotechnology company that develops fertility treatments, plans to use Crispr to correct gene disorders in human eggs. In April, researchers at Sun Yat-Sen University in Guangzhou, China, said they had used Crispr to try to repair a flawed gene in human embryos that’s responsible for a form of thalassemia. The researchers attempted the procedure in more than 80 embryos that were never viable. A handful successfully adopted the replacement gene; unexpected mutations occurred in others.
Crispr could encourage editing of all kinds of genomes that, if unsupervised, may present unanticipated risks, says Arthur Caplan, head of medical ethics at New York University School of Medicine. The technique could be used to try to amplify genes thought to boost intelligence in adults. Use on animals and insects could also lead to ecological havoc, Caplan says. “You could have a disaster on your hands, and you don’t have to touch a human to do it,” he says.
Scientists have called for a moratorium on the use of Crispr in human sperm, eggs, and embryos, known as the human germline. The National Institutes of Health in late April said the agency won’t fund any gene-editing work on human embryos. “We’re not making designer babies,” says Katrine Bosley, Editas’s chief executive officer.
The concerns might discourage further Crispr investment, says Jay Lichter, managing director of Avalon Ventures, a fund based in La Jolla. He’s wary of new regulations and protocols because they could restrict a broader range of experiments, even those by companies such as Editas that pledge not to use Crispr on the human germline. “The regulators and the politicians are going to be all over this if anyone tries to move too fast,” says Dr. Robert Lanza, chief scientific officer of Ocata Therapeutics, a biotechnology company using stem cells to treat eye disease.
Fears of meddling with DNA often arise when new gene technologies are introduced, says George Church, a Harvard geneticist and an Editas founder. The debate over Crispr is important, he says, because the technique is powerful and useful. Church is separately researching how Crispr could be used to counter the effects of aging.
Topol says the technology’s potential must be investigated. “There are a number of conditions, like hemophilia and HIV, that this might help treat,” he says. “There’s a lot of excitement.”
The bottom line: Ethical concerns about the use of a gene-editing technique could slow development of promising treatments.