New medical treatment – correction of a patient’s genetic mutation
Author:Science and Technology Division, UK
Article Source:The Medical Research Council, 13th Oct. 2011
Publish Date:2012.02.21
A research led by researchers from the Wellcome Trust Sanger Institute and the University of Cambridge has, for the first time, successfully corrected a human gene mutation in a patient’s stem cells. The result brings the possibility of patient-specific therapies closer to becoming a reality.
The research targeted a gene mutation responsible for both cirrhotic liver disease and lung emphysema. The condition is the commonest known inherited lung and liver disorder, occurring in about one in 2,000 North Europeans. Alpha1-antitrypsin gene is responsible for making a protein in the liver that protects against excessive inflammation. When alpha1-antitrypsin gene is mutated, the protein can’t be released properly and it becomes trapped in the liver, eventually leading to cirrhosis and lung emphysema.
The new research worked on human induced pluripotent stem cells (hIPSCs) with the mutated gene. By using “molecular scissors” to snip the genome at precisely the right place, the researchers then inserted a correct version of the gene using a DNA transporter called piggyBac. The piggyBac sequences were subsequently removed from the cells, allowing them to be converted into liver cells without any trace of residual DNA damage at the site of correction. The scientists then proved that the accurate copy of the gene was active in the liver cells they had produced by demonstrating the presence of normal alpha1-antitrypsin protein.
The scientists explained that there is currently no cure for this disease other than liver transplantation and given the increasingly strains being placed on the national liver transplant programme as a result of the sharp increase in the frequency of liver disease, alternative therapies for genetic and other liver diseases are urgently being sought. Human induced pluripotent stem cells can be converted into a wide range of tissues. Using cutting-edge methods, the new research was able to correct stem cells with the mutation and then re-introduce the corrected cells into human bodies. It does not only fix the mutation that causes the disease, but also do this with the patient’s own cells, thereby avoiding any immune injection. It is hoped that this new research will lead to personalised cell therapy for genetic disorders in the near future.