{
  "abstract": "Gene therapy aims to replace or repair a defective gene, thus impacting the genetic expression. Gene editing can occur in three ways: replacing a mutated gene with a healthy copy of the gene, inactivating a mutated gene or introducing a new gene into the body. There are now good examples of gene editing in haemophilia, cystic fibrosis, HIV and muscular dystrophy. What about the haemoglobinopathies? Hana R et al (N Engl J Med 2026;394:1281-1291. DOI: 10.1056/NEJMoa2415550) have looked at the clustered, regularly, interspaced, short, palindromic repeats (CRISPR) -Cas12a gene editing of HBG1 and HBG2 promoters. This focuses on treating sickle cell disease, using renizgamglogene autogedtemcel (known as reni-cel) which is a CRISPR gene-edited autologous haematopoietic stem-cell therapy. The therapy disrupts the BCL11A binding sites in the HBG1 and HBG2 promoters and reactivates foetal haemoglobin production. They conducted a phase 1-2, multicentre, open-label, single-group study involving 28 patients with severe sickle cell disease who were 12–50 years of age. Treatment with reni-cel led to normalisation of the total haemoglobin level and an increase in the percentage of foetal haemoglobin, with no vaso-occlusive events occurring in 27 of 28 patients after infusion. Frangoul H et al (N Engl J Med 2026;394:1292-1301. DOI: 10.1056/NEJMoa2501277) examined reni-cel therapy for transfusion-dependent β-thalassaemia. They completed a phase 1-2, multicentre, open-label, nine participants with transfusion-dependent β-thalassaemia (four β0/β0 or β0/β0-like and five non-β0/β0 genotypes) aged 18–35 years of age. Every participant had neutrophil and platelet engraftment by 42 days after infusion. Six participants who could be evaluated at 12 months or later were transfusion independent. The mean total and foetal haemoglobin levels were greater than 12g per dL and greater than 11g per dL, respectively, between months 6 and 18. Treatment with reni-cel clearly resulted in rapid neutrophil engraftment, an increase in fetal haemoglobin expression and transfusion independence. Franco Locatelli F (N Engl J Med 2026;394:1338-1340. DOI: 10.1056/NEJMe2602194) supplies the editorial and the perspective. There is a description of the epidemiology and historical journey of the treatments for these two diseases. The editorial highlights the urgent need for the development and validation of accessible, curative treatments that will give patients independence from transfusions and reduced episodes of severe vaso-occlusive crises. He describes allogeneic haematopoietic stem-cell transplantation and the concern for identifying HLA matched donors, which has been the only option. Franco describes gene therapy as the attractive option, particularly for those without a matched HLA typed donor. He describes these studies and a useful table summarises three possible treatments. The studies have been in young adults from the age of 12 years into adulthood. There is a good description of the limitations of these studies, the inevitable small samples and short duration of study. Both papers report their adverse events, but clearly longer-term safety data needs to be generated. There is exciting promise here, so Archivist is sure these studies will be coming. Watch this space!",
  "authors": [
    {
      "affiliations": [],
      "name": "BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health"
    }
  ],
  "title": "Gene editing for haemoglobinopathies",
  "uid": "4c362b78-a9f5-547a-8267-4091e467267f"
}