Safe way to repair sickle cell disease genes developed
Sickle cell disease is a group of inherited blood disorders caused by genetic mutations in the beta-globin gene, resulting in abnormal haemoglobin. Red blood cells become hard, sticky and sickle-shaped, with reduced ability to carry oxygen. Symptoms of sickle cell disease include swelling of the hands and feet, pain due to clogging of blood vessels, anaemia and stroke. The disease can be cured with stem cell or bone marrow transplants, but there is a high risk that recipients of transplants will reject the donated marrow or cells, which can result in serious side effects and even death.
Researchers at the Salk Institute for Biological Studies in the US have now developed a way to use patients’ own cells to potentially cure sickle cell disease and many other disorders caused by mutations affecting haemoglobin. To do that, they used a two-step approach. First, they took adult skin cells from a patient with a beta-globin mutation that causes sickle cell disease. They used six genes to coax these cells to revert to iPSCs, which could then be developed into blood cells. The genes were introduced into the cells using a technique that avoids the use of viruses and insertion of transgenes into the cells’ genome. Their next step was to repair the beta-globin gene mutation in the stem cells. To swap the defective gene with a normal copy in the iPSCs, the investigators used a modified adenovirus that, unlike viruses used in other methods, does not replicate itself in the body and does not alter the host cells’ DNA. The viral genes were deleted and replaced with a DNA sequence that contained a normal beta-globin gene. The modified virus then delivered the new genetic material inside the iPSCs, where the DNA region containing the broken gene was replaced with the sequence containing the normal gene. By replacing a relatively large region of DNA, the technique allows many gene mutations to be repaired at once.
