For the first time, scientists have cleanly corrected a human gene mutation in a patient's stem cells. The result, reported in Nature on Wednesday 12 October, brings the possibility of patient-specific therapies closer to becoming a reality.
The team, led by researchers from the Wellcome Trust Sanger Institute and the University of Cambridge, targeted a gene mutation responsible for both cirrhotic liver disease and lung emphysema. Using cutting-edge methods, they were able to correct the sequence of a patient's genome, remove all exogenous DNA and show that the corrected gene worked normally.
The researchers used human induced pluripotent stem cells (hIPSCs) for their research because, once reprogrammed in the Petri dish, these cells can be converted into a wide range of tissues. If stem cells from a patient with a gene defect can be corrected, scientists believe that when reintroduced into the patient they could treat the effects of the mutation causing the disease. To make such a hope reality, efficient methods of introducing DNA, repairing the gene, removing all foreign DNA and verifying the changes are needed.
For this research, the team looked at a deficiency caused by a mutation in alpha1-antitrypsin, a gene that is active in the liver where it is responsible for making a protein that protects against excessive inflammation. People with mutant alpha1-antitrypsin cannot release the protein properly from the liver, where it becomes trapped, eventually leading to liver cirrhosis and lung emphysema as a consequence. This is the commonest known inherited disorder of the liver and lung, occurring in about one in 2000 people of North European origin.
Building on previous work from Cambridge which showed that it was possible to transform skin cells into liver cells by reprogramming stem cells, the team successfully and accurately corrected an alpha1-antitrypsin gene in an established cell line containing the mutation.
|Contact: Don Powell|
Wellcome Trust Sanger Institute