Scientists in the US have used a genome-editing technique to partially restore vision in blind rats.
This is the first time that such techniques have been used to add genetic code to the genomes of adult cells which have stopped dividing. Previously, the CRISPR/Cas9 system could only be effectively used in dividing cells, such as stem cells and some adult cells like skin and gut.
'We now have a technology that allows us to modify the DNA of non-dividing cells, to fix broken genes in the brain, heart and liver,' said Professor Juan Carlos Izpisua Belmonte of the Salk Institute, California, and lead author of the study. 'It allows us for the first time to be able to dream of curing diseases that we couldn't before, which is exciting.'
In the study, published in Nature, the researchers used a modified version of the CRISPR/Cas9 system of genome editing. After cutting the DNA in a cell and inserting replacement DNA, the genome-editing process normally relies on a DNA-repair mechanism present in all dividing cells to re-join the DNA strand ends. However, some adult cells such as those of the eye, brain, or heart do not divide so cannot use this mechanism.
The team used a different DNA-repair cellular pathway, 'non-homologous end-joining' (NHEJ) found in adult cells, and paired it with an updated way of inserting replacement DNA, called homology-independent targeted integration (HITI) – delivering this package of molecular tools to the target cells using a modified virus. The result demonstrated that new genes could be inserted into adult nerve cells in the lab, and also into the brain cells of living adult mice.
'Using this NHEJ pathway to insert entirely new DNA is revolutionary for editing the genome in live adult organisms,' said Dr Keiichiro Suzuki of the Salk Institute and one of the paper's lead authors. 'No one has done this before.'
Finally, the researchers used this technique on rats which had a genetic mutation in the Mertk gene, expressed in the eye. In these rats, cells in the light-sensitive retina at the back of the eye die and vision is lost. This is similar to the inherited human disease retinitis pigmentosa.
Rats which were treated with the HITI system to introduce the correct Mertk gene showed increased production of the healthy form of Mertk protein in some cells, and an increase in their visual function. The researchers wrote however that 'the rescue was only partial and not enough to completely restore vision'.
Dr Andrew Wood of the University of Edinburgh, who was not involved in the work, said: 'This study is a really exciting development for therapeutic applications of genome editing. Before it can be applied to humans, it is now important to improve the efficiency with which the genome-editing molecules can be delivered to the relevant cells.'
On Wednesday 7 December 2017, genome editing and embryo research will be debated at the Progress Educational Trust's public conference 'Rethinking the Ethics of Embryo Research: Genome Editing, 14 Days and Beyond'.