Gene therapy project in Granada

This project is the first to be given a grant by the A-T research fund which is jointly funded by the A-T Society, Action for A-T and Sparks.The grant has been made to Professor Ignacio Molina of the University of Granada for a project focusing on the pre-clinical development of gene therapy for A-T.

Gene therapy involves using DNA – the material of which genes are made up – to treat a condition, rather than conventional drugs. In this case, the long-term aim is to try to insert a length of ‘corrected’ DNA into cells in the cerebellum of the person with A-T to replace the mutated DNA which they have inherited. The details and science of this approach to treatment are extremely complex and the path to developing treatments is a long one. This explanation will however try to keep things simple.

The gene therapy project which we are funding with Professor Molina and his team is not the beginning of the process but is based on work that he has already carried out.

 Minigene and vector

To date, they have both developed a corrected minigene – effectively a compact but functional replacement version of the gene which doesn’t work in someone with A-T – and a vector, that is a mechanism for transporting the minigene into cells.

The vector that they have developed is a so-called ‘lentiviral’ vector. The team have been working on lentiviral vectors for some years now and have developed their own vectors, with improved bio-safety features.

The project and its challenges

They have successfully used the vector to insert the ATM minigene into cells taken from patients with A-T and have also demonstrated that the minigene is expressed within the target cells. This means that they have been successful in getting the cell to produce a protein. However, what they do not yet know, is whether this protein is fully functional.

In spite of what the term ‘minigene’ may suggest, the A-T minigene is far from small (in gene terms at least). That is because the full version of the A-T gene is itself a very big gene. Genes are measured in kilobases (kb) and while a normal minigene will probably be in the region of 1.5 - 3 kb, this one is around 9 kb in size.

This is very close to the limit of what a lentivirus will carry, which creates problems. In particular, as the size of the gene increases, it gets more and more difficult to produce the loaded vector. So finding ways to improve the production of the vector is another challenge facing the team.

Assuming that they are able to overcome these challenges – that the protein is functional and it is possible to produce the vectors in sufficient quantity. The next issue will be bio-safety. Before you can even think of trying this approach on humans, there are a lot of safety questions which will need to be answered.

Nevertheless, the team are very optimistic about their work and very grateful to the A-T Society and the other charities for the support for their work.


Purkinje cells in the cerebellum

Purkinje cells in the cerebellum. One of the ultimate targets for the gene therapy project.


Professor Molina

Professor Ignacio Molina, who is leading the project.