Gene Therapy

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Gene Therapy is a research technique where the underlying genetic basis of a disease is addressed in order to treat or prevent a disease.

There are a few ways this can be done including:

  • introducing a “healthy” copy of the faulty gene – an approach commonly adopted for ‘recessive’ diseases where often there is a deficiency due to the genetic fault. This is the case in Stargardt’s disease (STGD1).
  • “switching off” the faulty gene that in ‘dominant’ disease is often producing a toxic product causing harm.

A phase I/II clinical trial of gene therapy to replace a normal copy of the gene that causes Stargardt’s disease, ABCA4, is currently underway.

Sanofi are conducting the trial, which is taking place in Portland, USA (Oregon Health and Science University) and Paris, France (Centre National d’Ophtalmologie des Quinze-Vingts).

A healthy copy of the gene is being surgically administered under the retina with the use of a vector in the form of a virus, which will carry the healthy copy of the ABCA4 gene and deliver it to the light sensitive cells, the photoreceptors, in the outer retina.

There have been no safety concerns to date, with some evidence of benefit in a small number of patients with early mild Stargardt disease. The trial is on-going.

More information can be found at:

Alternative Genetic Therapy Approach

In some cases of Stargardt disease, no faults can be found in the sections of the ABCA4 gene that code for the building block ‘ingredients’ of the ABCA4 protein, meaning that there are no clues to guide scientists in the development of treatments. Profs Frans Cremers and Rob Collin, at Radboud UMC in The Netherlands, are leading a team searching for hidden genetic faults in these cases.

A regular genetic test only examines part of each gene, disregarding non-coding sections known as ‘introns’. These sections are ‘edited out’ during protein construction by a process known as splicing. However, genetic faults within introns can still have a significant influence on how the coding regions are edited and interpreted by the cell’s protein-building machinery, often resulting in a faulty protein.

The researchers have developed a fast, cost-effective method of scanning the entire length of the ABCA4 gene, including the introns. The team’s new method has enabled them to find several intronic faults and they have gone on to develop a kind of molecular patch, described as a “band aid”, to cancel the harmful effects of these intronic genetic faults, and result in normal protein being made again. Such 'genetic editing' approaches are particularly applicable to intronic genetic faults.

The band aid is made from a synthetic form of RNA, the molecule that acts as an intermediary to translate the genetic code in DNA into proteins. It is delivered to the retina via an injection into the eye. However, each different genetic fault requires its own specific band aid, so obtaining a genetic diagnosis will be essential to potentially benefit from these treatments in future.