The revolutionary CRISPR gene editing tool has been used inside the human body for the first time in a landmark clinical trial to try and cure an inherited form of blindness called Leber’s congenital amaurosis (LCA).
CRISPR is a technique that involves using particular stretches of RNA to direct an endonuclease called Cas9 to a genomic region, where Cas9 cuts the DNA in a targeted and specific manner. It is an amazingly versatile and powerful technique and its ability to efficiently cut DNA has been demonstrated in a huge number of different cells, including in living mice and in cultured human cells. However, its effectiveness has not yet been proven in living humans.
The patients in the study have a mutation in a particular gene that is responsible for the production of proteins that play an important role in the photoreceptors in the human eye. People born with this mutation typically exhibit severe loss of vision in the first years of their life. Treatment of LCA is unfortunately not amenable to standard gene therapy because the gene responsible is simply too large to be replaced by a healthy copy.
Instead, the CRISPR components being used in this trial have been designed to target and cut DNA either side of the mutation causing the LCA blindness. The hope is that by injecting these components directly into a patient’s eye, CRISPR will cut the DNA either side of the mutation and then the cells’ own machinery will join the cuts back together in a way that results a healthy gene and improves the patient’s vision. This human trial follows earlier preclinical work demonstrating productive gene editing in mice.
This new trial adds to a small but growing number of gene editing treatments that are being investigated across the world. The first ever human gene editing trial began in 2017 and utilises zinc finger nucleases, rather than CRISPR, to try and treat the genetic disorder Hunter syndrome. One of the benefits often associated with CRISPR technology is the versatility and ease of design in order to target genes. However, there are still a number of unknowns associated with CRISPR as a therapeutic and one of the early goals of this trial will therefore be to assess whether CRISPR can safely be used in humans.
While this is the first report of an approved clinical trial being carried out using CRISPR, dramatic claims were made in 2018 that the first genetically edited babies had been born in China using this technique. At the time, there was widespread criticism and concern that this experiment had been carried out without appropriate ethical and regulatory approval. Earlier this year it was reported that the scientists responsible for creating these CRISPR-edited babies had been jailed for “illegal medical practices”. Carrying out the present trial under the watchful eye of regulatory authorities will alleviate a number of the concerns that scientists previously raised concerning the unregulated creation of gene edited babies.
Although still at a very early stage, this trial holds great promise for the treatment of LCA and for the use of CRISPR and other gene editing tools as therapeutics. If successful, this trial could help spur future development for treatments for a wide variety of genetic diseases such as cystic fibrosis and Huntington’s disease.
