The concept of gene editing has once again attracted media attention when researchers in the US recently reported having successfully corrected a dominantly inherited gene mutation in the human embryo. Using CRISPR/CAS9, a naturally occurring DNA editing process that bacteria use to disable viruses, researchers were able to promote the embryo’s own repair mechanisms to edit and correct a defect in a gene which can give rise to a potentially fatal cardiac condition.
With this story fuelling interest around gene editing, what potential does it hold for people living with genetic retinal conditions? Researchers are already exploring ways to use it to remove and replace the mutated genes responsible for retinitis pigmentosa and other gene-based forms of vision loss. For example, last year we shared news of the first reported correction of a genetic retinal disease gene in stem cells by the CRISPR/Cas9 gene-editing system. Using stem cells derived from a patient who donated a skin sample for the research, scientists managed to correct a defect in the RPGR gene associated with X-linked retinitis pigmentosa (RP) in approximately 13% of the patient stem cells. Editas, a gene editing company is developing a CRISPR/Cas9 therapy for LCA10 caused by a mutation in the CEP290 gene and are working toward a clinical trial for the therapy.
Also in recent months, scientists from Massachusetts have prevented the growth of blood vessels in the retina (termed angiogenesis) in mice using CRISPR/Cas9 technology. Angiogenesis is a feature of wet age-related macular degeneration (AMD) and this study highlights how it may be possible in the future to use CRISPR/Cas9 gene editing to prevent this form of AMD.
CRISPR/Cas9 technology is also being explored in Ireland. Fighting Blindness-funded researcher Professor Breandán Kennedy, who recently spoke on Drivetime Radio 1 about CRISPR describing it as “fine-detailed, targeted cutting of DNA”, is currently evaluating this technique in the context of sight loss. His team recently published a review which noted how gene editing may offer a potential alternative to gene therapy. Traditional gene therapy is used to add “corrected” versions of genes whereas gene editing sets about fixing the underlying defect within the gene. Traditional gene therapy has proven challenging to deliver genes such as the ABCA4 gene associated with Stargardt disease to the retina because of their large size. Gene editing offers a huge potential for conditions which are limited by current technologies.
Despite the exciting advances being made using gene editing, this technology is still in development and further work is needed to fully test this approach in humans. Caution must be advised until it is fully evaluated and validated for use in the clinic. At this point, careful thought must be given to ethical concerns, for example when and in which cells should gene editing occur. Consideration must also be given regarding permanent changes to human DNA. The prospect of being able to precisely target disease-causing genes is promising, but the scientific and patient community must agree to air on the side of caution until decisions are made about its safe and acceptable use.