The protein hemoglobin carries oxygen from our lungs to our tissues. Mutations in the genes that encode the protein chains that form hemoglobin can cause inherited blood disorders like sickle-cell anemia, or the so-called Thalassemias. Thalassemias come from the Greek word from sea (θάλασσα or thalassa), because these blood disorders are found in Mediterranean populations. Thalassemias are found in these populations because they convey some resistance to malaria, which was endemic to that area. People with thalassemias tend to have fatigue, weakness, a pale appearance, yellow discoloration of skin (jaundice), facial bone deformities, slow growth, abdominal swelling, or dark urine, although some people have no symptoms.
Now this common genetic blood disorder has been genetically corrected in cultured induced pluripotent stem cells by using cutting-edge genome-editing techniques.
β-Thalassaemia shows reduced levels of hemoglobin, and these reduced levels are due to mutations in the gene that encodes the β-globin protein. Hemoglobin consists of four protein chains, two of which are alpha-globin proteins, and the other two of which are beta-globin proteins. Mutations in the beta-globin gene reduces the levels of functional beta-globin protein and this reduces the levels of functional hemoglobin.
Yuet Kan and his colleagues at the University of California, San Francisco, made induced pluripotent stem cells from skin fibroblasts from a person who suffered from β-thalassemia. Kan and his colleagues then used the CRISPR–Cas9 gene-editing technique to correct the mutation responsible for β-thalassemia. The CRISPR–Cas9 gene-editing technique allows for precise and accurate correction of the mutation without affecting other genes.
After the genetic editing, the iPSCs were differentiated into the precursors of red blood cells in culture and demonstrated that the modified cells showed higher expression of hemoglobin than unmodified cells.
Hopefully transplantation of such corrected cells back into the original patient could one day provide a cure for β-thalassaemia, according to the authors.