Of all the advances that scientific and technological development has brought in the field of hereditary pathologies that affect vision, the most relevant and transcendent for the patient is the possibility of applying treatments for diseases that, until now, were considered incurable. . 30 years ago a new type of therapy was successfully started: gene therapy.
In general terms, gene therapy is the introduction or modification of genetic information in the patient, with the aim of relieving or reversing their symptoms. Gene therapy can be applied by different methodologies. These are, to date, the most promising in the field of hereditary retinal dystrophies:
This therapy introduces a healthy copy of the affected gene into the patient’s cells using viral vectors or nanoparticles. This is currently the most advanced therapeutic strategy and is being applied in various trials. However, it has two main disadvantages. For one thing, there is a limit to the size of the gene that can be introduced. On the other hand, it is not an effective strategy in dominantly inherited diseases.
Gene editing: CRISPR-Cas
The CRISPR-Cas system allows direct modification of the patient’s affected genes. This system aims to introduce a sequence into the patient’s cells that is incorporated in the same place as the affected gene, and the information for the synthesis of an enzyme that will cut all or part of the defective gene. The EDIT-101 therapy from Editas Medicine Inc. thus removes part of the defective intron of the CEP290 gene.
Mutated genes generate messenger RNA from which defective proteins will be generated. Antisense oligonucleotides bind to these messenger RNAs, facilitating their degradation and blocking the production of defective proteins.
This technique consists of the use of light to activate therapeutic compounds. A recent therapy developed by Nanoscope Therapeutics Inc. introduces genes whose proteins, in combination with special glasses, are capable of responding to light signals and activating the neuronal circuitry responsible for vision.
Inteins are a type of protein capable of self-processing. That is, they can make cuts and joins from certain sequences, until a functional protein is obtained. The company SpliceBio is developing a therapy for the treatment of Stargardt’s disease caused by mutations in the ABCA4 gene, which is too large to be introduced in its entirety by means of traditional vectors, based on this strategy.