The study, published in Scientific Reports, used CRISPR/Cas9 to correct a mutation in cells derived from patients with retinitis pigmentosa (RP), thereby creating a source of therapeutic cells with a very low risk of rejection.
'Our vision is to develop a personalised approach to treating eye disease,' said study co-author Dr Stephen Tsang of Columbia University Medical Centre. He added, 'We still have some way to go, but we believe that the first therapeutic use of CRISPR will be to treat an eye disease. Here we have demonstrated that the initial steps are feasible.'
RP is a genetic disorder affecting approximately 1 in 4000 people, in which light-sensing cells in the retina degenerate, resulting in tunnel vision and eventually total sight loss. Currently, there is no cure for RP although recent gene-therapy and stem-cell studies have shown some promise (see BioNews 603 and 784).
The team reprogrammed skin cells to become induced pluripotent stem cells, and then used CRISPR/Cas9 to pinpoint and repair a defective mutation in the RPGR gene, which causes the aggressive X-linked variant of RP. 'The X-linked form of retinitis pigmentosa is an ideal candidate for a precision medicine approach because a common mutation accounts for 90 percent of cases,' Dr Tsang explained.
The team was not sure whether the CRISPR technology would be able to home in on and correct the genetic mutation since it sits in a highly repetitive sequence of the RPGR gene, making it difficult to discriminate from one region from another. Despite these difficulties, they were able to correct the genetic mutation in 13 percent of the stem cells.
The researchers say that the present study is an important proof-of-concept, demonstrating personalised and precision medicine through the repair of a mutation using genome-edited stem cells. Non-CRISPR gene therapies are undergoing clinical trials but these do not permanently correct the defective gene, and initial gains in retinal sensitivity gradually diminish over time.
Dr Tsang said that there is more work to do before clinical trials can begin using the technique. 'Before we go into patients, we want to make sure we are only changing that particular single mutation, and we are not making other alterations to the genome,' he said.