Fix the hemoglobin gene
In Europe, for the first time, they plan to use CRISPR for the treatment of congenital blood disease
Anton Bugaichuk, Naked Science
CRISPR Therapeutics has developed a method to cure beta-thalassemia using gene therapy.
Thalassemia is a congenital hemoglobinopathy: the synthesis of proteins that make up the structure of hemoglobin is suppressed, which leads to the destruction of red blood cells. The hemoglobin of an adult individual is 97% hemoglobin A (HbA), consists of two α- and two β-monomers. The HBB gene encodes the β-chains of the protein; when the gene is damaged, fetal hemoglobin HbF, which normally the fetus produces before birth, displaces HbA. In an adult, fetal hemoglobin is unable to carry oxygen, resulting in oxygen starvation of tissues (hypoxia).
With the mutation of one allele, a small thalassemia occurs – a mild disease. If the damaged gene is obtained from both parents, then the child becomes ill with a severe form – large thalassemia. Characteristic symptoms: anemia, pathological changes in bones, impaired liver and spleen (hepatosplenomegaly occurs). Patients with large thalassemia should have blood transfusions twice a month, take a lot of medications, and the prognosis is unfavorable: death usually occurs in infancy or somewhat later.
A minor form of the disease increases resistance to malarial plasmodia (similar to sickle cell anemia), and thalassemia is common in regions with malarial foci. The name means "anemia of the seashore", as the disease occurs in the Mediterranean and Black Sea regions. The incidence in Azerbaijan is observed in 7-10% of the population. In the world, 300 thousand children receive this diagnosis every year.
The cure requires the restoration of normal oxygen transport in the body, that is, it is necessary to suppress fetal hemoglobin and produce hemoglobin A.
To do this, the researchers proposed using CRISPR (clustered regularly interspaced short palindromic repeats). The mechanism works similarly to the "find and replace" operation of the text editor: The Cas9 enzyme cuts the DNA at a location "selected" from the sample. The defective segment of DNA is removed, and a healthy one "grows" instead.
DNA editing by CRISPR/Cas9 / © Reuters, Nature
For the treatment of thalassemia, scientists suggest taking stem cell samples from patients and processing them in the laboratory, correcting genetic defects in the described way. The second stage is the transplantation of stem cells to the patient using blood transfusion. Doctors believe that the "corrected" cells will begin to produce healthy hemoglobin A. If the technique works, beta-thalassemia will become the first disease in Europe to be cured by full-fledged gene therapy using the CRISPR method.
China has already conducted research on the method for the treatment of HIV and cancer. The University of Pennsylvania (USA) is also studying cancer gene therapy. The first person in the world to undergo gene editing is Brian Madeux from California, who suffers from Hunter's disease, a form of mucopolysaccharidosis.
The full results of the experiment are not yet known, but geneticist from University College London Helen O'Neill is confident of a positive result: "The therapy successfully corrected more than 90% of the patients' blood stem cells, which were then transfused back to them." It is important to check for no side effects, but "preclinical trials look very promising."
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