The human genome project, completed in 2003, allowed us to read the information stored in the human genome. Two decades later, gene editing, now enables not only to read, but also to edit the genome by precisely changing a single nucleotide out of the 3 billion base pairs. 
 

Base editing for Stargardt disease

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Stargardt disease is one of the leading causes of blindness in juveniles. The vast majority of the patients carry a mutation in the ABCA4 gene. The protein product of this gene is responsible for removing a toxic by-product produced upon normal visual function in the retina, the light sensitive layer at the back of the eye. Affected patients slowly lose their central vision, which severely impairs their ability to read, recognize faces or to see colors. Currently, there is no treatment available for this seriously debilitating disorder.

With the advent of gene therapy, it is possible to introduce, remove or change the genetic material in cells in order to treat diseases. Base editing, a novel but highly promising approach can directly change the faulty genetic code and revert disease causing mutations back to normal. This process is similar to correcting a single typo in a text. Base editors are complex molecular machines that are guided to the target gene of interest (ABCA4 in our case) via a small nucleic acid molecule.

Together with BEAM Therapeutics (Cambridge, MA, USA), IOB developed a base editing approach to treat Stargardt disease. We have demonstrated that base editing can correct the underlying mutation in the ABCA4 gene, with very high precision. We reached base editing correction rates up to 60% in cone photoreceptors, which is way above the threshold required for therapeutic level. It is expected that correction of ~20% of cones is expected to be therapeutic and provide significant visual benefit to patients. The direct genetic correction of the underlying genetic problem holds promise for patients with Stargardt disease and can be applied to other ocular diseases in the future.

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