For the first time, scientists at the Casey Eye Institute at the Oregon Health & Science University (OHSU) in Portland in the US have used CRISPR gene editing directly inside a person’s body, the trial sponsors announced on 4 March. Components of the gene-editing system were directly injected into the eye, near photoreceptor cells, in a bid to treat a rare inherited form of blindness.
The procedure has marked “a new era in medicine” using a technology that “makes editing DNA much easier and much more effective”, according to Dr Jason Comander, an eye surgeon at Massachusetts Eye and Ear in Boston.
The landmark clinical trial — named BRILLIANCE — is being carried out to test the ability of the CRISPR–Cas9 gene-editing techniques to remove the mutation that causes a rare condition called Leber congenital amaurosis 10 (LCA10). The treatment is.
If the therapy, which is being jointly developed by Editas Medicine, a pharmaceutical company based in Cambridge, Massachusetts and Ireland–based company Allergan, works as planned, scientists hope to test the treatment in 18 more people – both children and adults. But it could take up to one month to see the results.
“We literally have the potential to take people who are essentially blind and make them see”, Charles Albright, chief scientific officer of Editas Medicine, told the Associated Press.
This is the first time CRISPR has been used to edit human genes inside the body — referred to as in vivo gene editing — and is a significant jump from treating cells in a dish. Previous trials used CRISPR-Cas9 to edit cells outside the body, which were then infused back into the body of the patient.
An older gene-editing technique, called zinc-finger nucleases, was the first-ever gene-editing technique to be used directly in the body to treat a rare metabolic condition called Hunter’s syndrome. Early results suggest that, although safe, the treatment is doing little to alleviate symptoms of the disorder. But many scientists believe CRISPR is a much better and more precise tool.
Leber congenital amaurosis is caused by a mutation in the CEP290 gene that disables light-sensing photoreceptor cells in the retina, leading to blindness early in childhood. Scientists hope that since these cells are still present in people with the disease, gene therapy could be used to “reactivate” them.
However, the CEP290 gene is too large for conventional virus-based gene therapies and will not fit into a viral genome. And that’s where CRISPR comes in. Instead of completely replacing the gene, the scientists are using CRISPR-Cas9 to directly delete the mutation and restore vision. Furthermore, the approach is designed to be permanent and will not be passed on to the offspring.
“Being able to edit genes inside the human body is incredibly profound”, said Prof Mark Pennesi of the OHSU School of Medicine, who is leading the trial.
“Beyond potentially offering treatment for a previously untreatable form of blindness, in vivo gene editing could also enable treatments for a much wider range of diseases”.