This article is taken from the monthly Sciences et Avenir – La Recherche n°908, dated October 2022.

To treat certain diseases (essentially genetic diseases where only one gene is affected), scientists have been developing powerful tools since the 1990s aimed at repairing or replacing faulty genes or organs. If it is a faulty gene responsible for the patient’s disease, as is the case for example with a disease such as beta-thalassemia, which produces abnormal hemoglobin resulting in severe anemia, the therapy consists of introduce a normal version of the gene in question into the patient’s cells. In this way, the patient’s body becomes able to manufacture the protein whose failure or absence causes the disease.

A disappointment in the 2000s

The operation requires that the bad gene be known and identified beforehand. But this is not the most delicate stage, since it is then necessary to associate the gene-drug with a vector so that this one allows it to penetrate into the cell. Most often, this vector is a virus whose cellular “wall-passing” abilities are exploited. Alas, this approach is sometimes accompanied by significant undesirable effects.

In the 2000s, Inserm and Necker Hospital (Paris) conducted therapeutic trials on bubble children suffering from serious deficiencies in their immune system. Immune stem cells were taken from the marrow of the young patients and genetically modified to express the missing gene, then injected back into their bloodstreams. While eight of these bubble children were successfully treated, this trial unfortunately triggered leukemia in several of them. In question, the vector used, an adenovirus, which implanted itself haphazardly in the body, awakening tumor genes.

Since this disappointment, the arsenal of vectors has greatly expanded and improved. It has made it possible to develop gene therapies for several diseases, including sickle cell anemia or, precisely, beta-thalassemia, the two most widespread monogenic diseases in the world. Regarding the latter, about thirty patients (in France, the United States, Australia and Thailand) have been successfully treated in recent years: they have been able to stop their monthly blood transfusions by producing, thanks to the treatment, a therapeutic hemoglobin .

The gene editing revolution

Gene therapy is now experiencing a new boom thanks to the CRISPR gene editing tool. Thus, still to treat beta-thalassemia, the results of an unprecedented trial were presented in 2020. It concerned ten patients from whom stem cells were taken, corrected in the laboratory with CRISPR, and reinjected. Again, it was a success and the patients were able to do without transfusions.

For most pathologies, unfortunately, there is not just one gene to be repaired but several, and gene therapy is then not enough. In this case, one of the promising avenues of research is to combine gene therapy and cell therapy: injecting patients with cells endowed with new properties. It is one of the chosen pathways to target and kill cancer cells.