Blind animals have had their vision partially restored using a revolutionary DNA editing technique that scientists say could in future be applied to a range of devastating genetic diseases.
The study is the first to demonstrate that a gene editing tool, called Crispr, can be used to replace faulty genes with working versions in the cells of adults – in this case adult rats.
Previously, the powerful procedure, in which strands of DNA are snipped out and replaced, had been used only in dividing cells – such as those in an embryo – and scientists had struggled to apply it to non-dividing cells that make up most adult tissue, including the brain, heart, kidneys and liver.
The latest advance paves the way for Crispr to be used to treat a range of incurable illnesses, such as muscular dystrophy, haemophilia and cystic fibrosis, by overwriting aberrant genes with a healthy working version.
Professor Juan Carlos Izpisua Belmonte, who led the work at the Salk Institute in California, said: “For the first time, we can enter into cells that do not divide and modify the DNA at will. The possible applications of this discovery are vast.”
The technique could be trialled in humans in as little as one or two years, he predicted, adding that the team were already working on developing therapies for muscular dystrophy.
Crispr, a tool sometimes referred to as “molecular scissors”, has already been hailed as a game-changer in genetics because it allows scientists to cut precise sections of DNA and replace them with synthetic, healthy replacements.
In stable cells in living organisms, however, the DNA is less accessible, and scientists had not managed to achieve the same “cut and paste” editing. This meant that while Crispr could potentially be used to remove genetic mutations from embryos it not clear whether it also could be harnessed as a therapy for children and adults with genetic disorders.
The latest study, published in the journal Nature, demonstrates that adult rats that had been engineered to have a genetic form of blindness called retinitis pigmentosa could be treated using Crispr gene therapy.
The condition, which affects about one in 4,000 people, occurs when a faulty gene causes retinal cells to gradually die off, leading to blindness. The scientists targeted the retinal cells by injecting a virus, carrying a package of gene-editing instructions, into the eyes of blind three-week-old rats.
When the rats were eight weeks old, the animals were shown to respond to light – although their vision was not fully restored – and they passed several tests indicating healing in their retinal cells.
“We were able to improve the vision of these blind rats,” said co-lead author Reyna Hernandez-Benitez, also of the Salk Institute. “This early success suggests that this technology is very promising.”
The treatment could be improved by being administered earlier, when less damage had been done, the scientists said. Before being used in humans, it would also need to be made more efficient, as only about 5% of cells had their faulty DNA replaced, the study found.
Professor Robert MacLaren, who works on gene therapy at the University of Oxford and was not involved in the research, said: “Getting the DNA into cells that are not dividing is quite an advance. This has got huge potential.”
However, he said that the authors’ predicted timeline for clinical trials was “extremely optimistic”, suggesting that more extensive safety studies would be essential first. “The potential drawback is that you’ve got something that goes around in cells snipping DNA. Assuming that safety studies show Crispr doesn’t damage healthy DNA, I think we could see this in clinical trials within five years.”