Since scientists first used CRISPR-Cas9 to edit living human cells in 2013, they have said that the possibilities for using it to treat diseases are practically endless.
Only in recent years, advances in CRISPR have been happening at breakneck speed - and several companies have emerged to commercialize the technology. Now patients in Europe and the U.S. can be treated with CRISPR-based therapies as early as 2018.
The hope is that CRISPR can be used in a single procedure to cure some of the most devastating inherited disorders and cancers, some of which have few or no current treatment options. Scientists want to deploy the technology to correct genetic errors in a person's DNA, getting to the root of the disease.
This may be the dream, but the reality is quite different. Researchers have already delayed the start dates of clinical trials. And the studies scheduled to begin in the next year or two will treat a small number of patients with some rare diseases. It will probably take years before the technology can be used for more common diseases and in more patients.
CRISPR Therapeutics, based in Cambridge, Massachusetts, became the first company to ask European regulators for permission to start a trial next year. The company will use gene-editing technology to correct a genetic defect in patients with beta-thalassemia, an inherited blood disorder.
Samarth Kulkarni, CEO of CRISPR Therapeutics, says the company is also planning to seek approval from the U.S. Food and Drug Administration in the first half of 2018 to start a CRISPR study for sickle cell disease.
About 15,000 people in Europe have beta-thalassemia and about 100,000 in the United States have sickle cells. Both are genetic disorders caused by mutations in the genes that produce hemoglobin, an important protein in red blood cells that carries oxygen throughout the body. Normally, both parents must pass on an abnormal gene for the child to develop the disease.
Researchers at Stanford University School of Medicine are also transferring a CRISPR treatment for sickle cell for clinical testing. Led by Matthew Porteus, an associate professor of pediatrics, the group will apply for FDA authorization in 2018 to begin a test the following year.
CRISPR Therapeutics and Stanford are taking different approaches. Both groups are extracting stem cells from patients' bone marrow and then altering them with CRISPR. But instead of trying to fix the defective gene in the sickle cell, CRISPR Therapeutics is using the editing tool to make the cells produce another protein, a children's version of hemoglobin. The modified cells would then be infused into patients. The company is using the same method to treat patients in Europe with beta-thalassemia.
In the Stanford sickle cell study, researchers will try to directly correct the mutation in the hemoglobin gene to convert sickle cells into normal cells.
Stanford will take the test at his new Center for Curative and Definitive Medicine. Maria Grazia Roncarolo, director of the new center, says that Stanford is planning to open “several genome editing trials” in the coming years. In addition to the sickle cell, Roncarolo says Stanford is planning additional CRISPR tests for metabolic, autoimmune, and neurogenerative diseases.
But while some trials are advancing, others are paralyzed. The University of Pennsylvania last year signaled its intention to initiate the first CRISPR study in humans. They obtained permission from the National Institutes of Health and the FDA to use CRISPR to treat melanoma, sarcoma, and multiple myeloma. The proposed test would involve removing T lymphocytes from patients, editing them in a laboratory, and infusing them with patients.
But when asked about the status of the test, a spokesman for the University of Pennsylvania told MIT Technology Review that she could not provide an update on when it would start. A handful of companies are also trying to modify T cells with CRISPR to treat cancer, but none of them have announced plans for clinical trials yet.
Editas Medicine, another company based in Cambridge, Massachusetts, also postponed the start of its first planned clinical trial of a CRISPR-based treatment for a type of hereditary blindness. The company said manufacturing problems with the therapy were responsible for the delay.
Intellia Therapeutics, another CRISPR startup, did not say when it plans to start clinical trials.
Meanwhile, several CRISPR studies are underway in China, all for different types of cancer, according to lists at clinicaltrials.gov. The researchers have not yet published the first results of these studies.
In the U.S. and Europe, 2018 may not be the year CRISPR devotees expected, but Alexey Bersenev, director of the Advanced Cell Therapy Laboratory at Yale-New Haven Hospital, says that in 2019 we will be able to see more than a dozen entries for new clinical trials.
“The field is currently quite optimistic about possible clinical trial results”, says Bersenev, who is also a co-founder of the celltrials.org database, which monitors cell therapy tests. "Every new and hot biomedical technology usually goes through a stage of exaggerated expectations." He says he would not be surprised if the investigators further delay the planned clinical tests.