(Bloomberg) -- Editing DNA with the same ease as spell-checking a Word document is a scientific holy grail. It would allow debilitating and deadly genetic diseases to not only be treated, but cured. The US Food and Drug Administration’s approval on Friday of the first treatment using the Nobel-prize-winning technology Crispr is a medical milestone that puts that dream one giant step closer to reality.
Two companies, Vertex Pharmaceuticals Inc. and Crispr Therapeutics AG, are now cleared to sell the cutting-edge gene-editing treatment to potentially cure sickle cell disease. But Crispr’s real potential — fixing problematic genetic code inside of the body instead of in a lab — is still in the future.
“I’m looking a few years ahead, to when we can transcend this milestone,” said Eric Topol, a physician-scientist and director of the Scripps Research Translational Institute. “This is just the beginning.”
The therapy from Vertex and Crispr Therapeutics is a potential game-changer for sickle cell patients — by editing DNA to fix flawed red blood cells, it could leave patients disease-free. But the approach used by the two companies is widely viewed as a less risky application of Crispr. Rather than edit the mutation that is responsible for the disease in the body, the therapy involves removing blood stem cells and editing them in a lab “ex vivo,” or outside the body. Ex-vivo editing is considered safer; scientists can make sure they haven’t accidentally edited the wrong bits of DNA before transplanting the edited blood stem cells back into a patient’s body.
For Crispr to reach its full potential and cure other diseases that affect the brain, heart, lungs and other organs, researchers will need to safely edit genes “in vivo,” or inside the body. In vivo therapies would also potentially be far less complicated and strenuous for the patients. For the newly approved therapy, dubbed Casgevy, patients undergo chemotherapy to remove cells from the bone marrow so they can be replaced with the edited cells. It’s a painful and strenuous process.
The Crispr therapy, along with another gene-therapy for sickle disease approved on Friday that uses a different technology, is no magic bullet, said Hank Greely, a law professor at Stanford University who wrote a book on the science and ethics of Crispr.
“They involve unpleasant and risky procedures,” he said. “Those methods have side effects, including often harming fertility by attacking ovaries and testicles.”
Crispr’s Nobel prize-winning innovation is the ability to cut and paste DNA with more ease and precision than ever before. Sickle cell, for example, was an early target for the technology because it’s caused by a mutation of just one single letter of genetic code. That mutation causes red blood cells to bend in a crescent shape instead of a round one, making it harder for essential oxygen to reach tissues and organs. The therapies extract blood stem cells and edit them in a lab, then return them to patients’ bodies. But more recent innovations to the technology, such as what’s known as prime editing, have made gene editing even more precise and efficient.“A one shot cure that’s not very pricey. That’s where this could go over time,” said Topol.
Companies that are pursuing such in-vivo treatments include Intellia Therapeutics Inc., which is studying a therapy for a rare swelling disorder, and Verve Therapeutics Inc., which wants to target cholesterol-raising genes. In 2012, scientists Jennifer Doudna and Emmanuelle Charpentier published work on Crispr that eight years later won them the Nobel Prize in chemistry. The FDA approval Friday is a major breakthrough for the technology that finally makes the innovation available to patients.
“This significant medical advancement holds tremendous promise for developing additional life-saving treatments and it gives hope to the millions of Americans who live with other rare diseases,” President Joe Biden said in a statement.
But before Crispr can reach its anticipated potential, there are tough questions to answer about affordability and safety.
“Sickle cell, though not ‘easy’ as a gene therapy, is much less difficult than most genetic diseases,” said Greely. “We understand it well, it has a relatively large population, and the editing can be done — and, importantly, checked — outside the body.”
On Friday, Vertex said the cost of its treatment would be $2.2 million per patient. That could reignite concerns about whether patients will be able to afford it. Many people who have sickle cell disease are on Medicaid, meaning cash-strapped states will need to decide whether they can afford to pay for hundreds – even thousands – of patients to get the one-time treatment.
And the safety risks of Crispr are not yet settled. The FDA said the companies have agreed to monitor patients who get the treatment for 15 years, a reminder that the new technology makes permanent changes to DNA and we don’t know the long-term impacts.“What are the long-term effects, and are they truly predictable?” Doudna, a Crispr pioneer, biochemist at University of California at Berkeley and founder of the Innovative Genomics Institute said in an October interview. “If they are, that bodes well for opening up the pipeline to other diseases in the future.”
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