Gene therapy of anemia
Two groups of researchers working independently of each other have succeeded in testing a gene therapy for sickle cell anemia. Both studies were published in the New England Journal of Medicine.
The first group included researchers from the USA, Germany, Canada and France; they used the CRISPR-Cas9 gene editing system to increase fetal hemoglobin production in patients with sickle cell anemia.
The second research group consisted of employees of Harvard Medical School and the Dana Farber Cancer Institute. They also sought to increase fetal hemoglobin production in patients with sickle cell anemia, but used a different method that involved delivery via a viral vector of RNA encoding the fetal hemoglobin gene.
Sickle cell anemia is a hereditary blood disorder that most often occurs in people of African descent. It is caused by a mutation in the hemoglobin protein gene. Changes lead to the fact that red blood cells lose elasticity and take a crescent shape. These cells can clog blood vessels, causing pain in the patient, and sometimes can lead to organ damage or stroke.
A high level of fetal hemoglobin in erythrocytes containing α- and γ-globins can improve the condition of patients by weakening the sickle-shaped polymerization of hemoglobin.
Both new treatment options were part of clinical researchers, and both were aimed at changing the genes responsible for the development of sickle cell anemia. In both cases, doctors took part of the patients' blood stem cells and deactivated the BCL11A genetic switch, whose operation is disrupted in this disease. The patients then received chemotherapy to destroy the defective cells, after which the edited stem cells were injected back into the blood of the patients. Over time, these stem cells turned into normal blood cells, and the symptoms of the disease disappeared.
Both groups were successful in their trials. Researchers using CRISPR-Cas9 conducted their first test about 17 months ago, and so far this patient has not had signs of pain associated with sickle cell anemia. Other patients showed similar results. The same group tested this method for the treatment of patients with beta-thalassemia, another hereditary disease in which little or no normal hemoglobin is produced due to mutations in approximately the same areas as in patients with sickle cell anemia. The second research group has tested its technique on six patients for several years and to date has not yet observed negative results. Clinical manifestations of sickle cell disease were reduced or absent during the entire follow-up period.
Both of these studies confirm the effectiveness of inhibition of BCL11A as an effective target for increasing fetal hemoglobin production and clinical recovery of patients with sickle cell anemia.
Articles by H.Frangoul et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia and E.B.Esrick et al. Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease is published in the New England Journal of Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru .