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Cut and paste

Researchers can now replace genes that cause diseases like retinitis pigmentosa in mature photoreceptors

DNA

Cutting out a faulty gene, such as the ones that lead to retinitis pigmentosa, and inserting a healthy version in an adult cell is the ultimate goal of gene editing – and an international team believes it has now achieved this.

The types of cell in the body that do not divide, including the photoreceptors in the adult retina, are a tough challenge for gene-editing scientists.

Up until now, they have been able to cut a faulty gene out of the DNA, but had to rely on one of the body’s natural repair mechanisms – which replaces the deleted gene with a copy from the undamaged second chromosome, rather than allowing new DNA to be inserted.

However, this type of repair only happens when a cell is dividing, and so could not be used in cells like photoreceptors.

Therefore, the researchers sought to take advantage of another type of natural DNA repair, a system that pastes a cut DNA strand together without any copying taking place.

By tweaking this process, the scientists were able to include a foreign piece of DNA – with the healthy version of a gene that when damaged causes retinitis pigmentosa – in the middle of the pasted strand of DNA in rats with the retinal disease.

These rodents were found to be able to respond to light, and researchers discovered evidence of healing in their retinal cells, in the paper published in the journal Nature.

California-based Salk Institute researcher, Dr Keiichiro Suzuki, described the feat as “revolutionary” and emphasised that: “No one has done this before.”

However, the current system only worked in approximately 4.5% of photoreceptors, fellow Salk Institute researcher, Dr Jun Wu, told OT.

He explained that: “With this efficiency, we detected improvement of rods and cones’ responses based on standard visual tests, but the rat can’t actually see.”

Therefore, the next step was to boost the effectiveness of the delivery, Dr Wu highlighted, adding: “We also expect, after optimisation in future studies, [a more efficient system] will help reverse the condition and fully restore vision.”

Research leader at the Salk Institute, Professor Juan Carlos Izpisua Belmonte, also emphasised that: “[This technology] allows us for the first time to be able to dream of curing diseases that we couldn’t before, which is exciting,” he concluded.

Image credit: Nogas1974