Researchers from Columbia University in the US have developed a new technique that uses CRISPR to restore retinal function in mice afflicted with the degenerative retinal disease retinitis pigmentosa.
This is the first time CRISPR technology has been successfully applied to an inherited disease known as a dominant disorder. The technique has the potential to work in hundreds of diseases in human patients, including Huntington’s disease, Marfan syndrome, and corneal dystrophies.
Dr Stephen Tsang and his colleagues aimed to create a more agile CRISPR tool that can treat more patients, regardless of their individual genetic profiles. Tsang calls the technique genome surgery because it cuts out the bad gene and replaces it with a functioning gene. Human trials are expected to begin in three years.
Tsang said: “Genome surgery is coming. Ophthalmology will be the first to see genome surgery before the rest of medicine.”
Retinitis pigmentosa is a group of rare inherited genetic disorders caused by one of more than 70 genes. It causes the breakdown and loss of cells in the retina. Typically, it strikes in childhood and slowly progresses, affecting peripheral vision and night vision. Most patients with this condition will lose much of their sight by early adulthood and become legally blind by age 40. There is no cure and it is estimated to affect one in 4,000 people globally.
Tsang and colleagues have come up with a better strategy to treat the autosomal dominant disease than previous attempts. Their approach allows them to cut out the faulty gene and replace it with a good gene, without affecting its normal function. The so called ‘ablate-and-replace’ strategy can be used to develop CRISPR tools for all types of mutations that reside in the same gene, which is especially helpful when many types of mutations lead to the same disorder.
For example, any one of the 150 mutations in the rhodopsin gene can lead to retinitis pigmentosa. Because Tsang’s technique can be applied in a mutation-independent manner, it represents a faster and more cost effective strategy for overcoming the difficulties associated with treating dominant disorders with genome surgery.
Another advantage of the technique is that it can be used in non-dividing cells, which means it could enable gene therapies that focus on non-dividing adult cells, such as those in the eye, brain, or heart. Until now, CRISPR has been applied more efficiently in dividing cells than non-dividing cells.