The US approves the first drug based on CRISPR technology, the genetic ‘cutter-paste’


The United Kingdom already gave the green light to this therapy for two blood diseases two weeks ago. It is expected that the European Agency will also rule on the matter soon.

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The characteristic sickle shape of erythrocytes in sickle cell disease.ILLUSTRATION: GABRIEL SANZ

The US regulatory agency (FDA, according to its acronym in English) approved this Friday the first drug based on CRISPR/Cas9, the tool that allows carrying out ‘genetic editing’. The drug has received the green light to correct the alteration in the DNA that causes sickle cell disease, a hematological disorder.

This is the second regulatory decision on this compound, after the recent approval of the British regulatory agency (MHRA), which occurred more than two weeks ago and which also contemplated its use in another blood disease, transfusion-dependent beta-thalassemia. The medication in question is Casgevy (exa-cel), from Vertex Pharmaceuticals.

The British agency was ahead of the US agency and the European EMA – whose advisory committee for Medicines for Human Use will also rule in a few weeks on this advanced therapy – when it came to endorsing this pioneering genetic treatment.

Is “a historic approval”in the words of the geneticist Kay Daviesfrom the University of Oxford, as it “opens the door to new applications of CRISPR therapies in the future for the possible cure of many genetic diseases.”

gene therapy exagamglogn autotemcel (exa-cel) uses the CRISPR/Cas9 genetic editing tool, the technology protagonist of the 2020 Nobel Prize in Chemistry, which the scientists received Jennifer Doudna and Emmanuelle Charpentier and which was developed thanks to the first discoveries made in bacteria by the Spanish Francis Mojica. Not even they imagined that the cut-paste genetically inspired by a defensive system of bacteria would reach the clinic so quickly. This is what Doudna recognized in Nature: “It was clear that having the ability to edit genomes was a powerful tool, but I don’t think any of us could have imagined how quickly this field would advance.”

Two pathologies with the same origin, but different

But CRISPR/Cas9 editing is not the only genetic strategy being explored to improve the survival and quality of life of people with sickle cell disease or transfusion-dependent beta-thalassemia.

In fact, this Friday, the decision adopted by the FDA also includes the approval of another medicine for the treatment of the same disease, Lyfgenia, from Bluebird Bio, through another variety of gene therapy: instead of CRISPR technology, it is based on the use of a lentiviral vector.

Both hemoglobinopathies have their origin in the beta subunit of hemoglobin.but actually They are different from each other: sickle cell disease (SCD) – a term that more closely defines this multisystem pathology than “anemia” – is caused by a mutation in the HBB gene that gives rise to hemoglobin S (HbS), whose polymerization gives erythrocytes the characteristic sickle shape; On the other hand, in beta-thalassemia, more than 400 different mutations that affect the HBB gene or regulatory regions and that generate the absence or reduction of normal hemoglobin (HbA).

In SCD or sickle cell disease, HbS causes destruction of red blood cells (hemolysis) and vasoocclusion, triggering acute episodes of very intense bone pain (vaso-occlusive crises) and chronic damage to multiple organs; In transfusion-dependent beta-thalassemia, as its name indicates, there is a requirement for periodic transfusionsgenerally several concentrates of red blood cells every three or four weeks.

Both diseases can be cured by allogeneic hematopoietic stem cell transplantation, although the right donor is not always found and the procedure carries risks. Hence the research in gene therapy has been seen as a option for that medical need, with both addition and editing strategies. Specialists remember that one of the main limitations of gene therapy will be its cost, which is estimated at around two million euros.

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