Correcting the genome
21 Nov 2011 by Evoluted New Media
Scientists have successfully and cleanly corrected a gene mutation in a patient’s stem cells, removing all traces of exogenous DNA before showing the corrected gene functions normally in test tube and mouse models. Once reprogrammed in a petri dish, stem cells can proliferate into a wide range of tissues, and researchers believe that if stem cells from a patient with a gene defect can be corrected, when reintroduced back into the patient they could treat the effects of the mutation causing the disease.
Researchers from the University of Cambridge and Wellcome Trust Sanger Institute targeted a mutation in alpha 1-antitrypsin in human induced pluripotent stem cells (hIPSCs).
The gene – active in the liver – is responsible for making a protein that protects against excessive inflammation. People with the mutant gene can’t release the protein, and eventually develop cirrhotic liver disease and lung emphysema.
Using molecular scissors, researchers snipped the genome at the precise place and inserted a correct version of the gene using piggyBac, a DNA transporter. The piggyBac sequences were then removed from the cells, allowing them to be converted into liver cells without any trace of residual DNA damage at the site.
“We have developed new systems to target genes and integrated all the components to correct, efficiently, defects in patient cells,” said Professor Allan Bradley, director emeritus of the Wellcome Trust Sanger Institute.
“Our systems leave behind no trace of the genetic manipulation, save for the gene correction. These are early steps but, if this technology can be taken into treatment, it will offer possible benefits for patients.”
The team proved that the accurate copy of the gene was active in the liver cells they had produced by demonstrating the presence of normal alpha 1-antitrypsin in test tube and mouse experiments.
They also took cells directly from a patient with alpha 1-antitrypsin deficiency and corrected the mutation as they had in the established cell line – the corrected cells produced normal alpha 1-antitrypsin protein. The next step will be exploring the use of the technique in human trials.
Nature: Targeted gene correction of alpha 1-antitrypsin deficiency in induced pluripotent stem cells
