Gene therapy, once hailed as a potential panacea for genetic disorders, has had a bit of a rocky ride over the last 20 years but recent experiments suggest that the way ahead may be smoother. Scientists at Stanford University in California have found a way to correct a faulty haemoglobin gene in patients with sickle cell anaemia, using some of the most recent advances in DNA technology.
Sickle cell anaemia is an inherited disease that distorts the shape of red blood cells, resulting in clogged up blood vessels and acute pain. Haemoglobin is the protein in red blood cells that carries oxygen and the warped blood cells die more quickly than normally – shaped blood cells, leaving sufferers short of oxygen and fatigued. In the UK, sickle cell anaemia affects more than 12,500 people and is the most common and fastest growing family of genetic disorders.
There is no cure and treatment relies on dealing with anaemia, increased susceptibility to infections and pain relief, with bone-marrow or stem cell transplants as a last resort for patients with severe disease. The disease has a recessive inheritance, such that it’s necessary to inherit two copies of a mutation in the haemoglobin Ggene, one from each parent. If each parent is a carrier, a child of these parents has a 50% chance of inheriting one copy of the mutated gene and becoming a carrier themselves, a 25% chance of being a carrier or a 25% chance of inheriting two copies of the faulty gene and having sickle cell anaemia.
In the latest study published in the journal Nature in November 2016, scientists corrected the faulty gene using a DNA cutting tool called CRISPR-Cas 9. This cuts out the faulty gene allowing its replacement with a healthy version from a donor. In mice experiments, the genetically-modified cells established themselves in the mice’s bone marrow cells producing healthy red blood cells. A senior author on the paper Prof. Porteus commented that now “we can take stem cells from a patient and correct the mutation and show that those cells turn into red blood cells that no longer make sickled haemoglobin.”
Although many early gene therapy trials have by and large been unsuccessful, expensive and sometimes even fatal, the use of new tools like CRISPR- Cas 9, is leading to a revival of interest. Now the CRISPR-Cas 9 modified gene therapy technique is set to be tested in human clinical trials for safety and then efficacy in sickle cell anaemia patients.