Clean correction of a patient’s genetic mutation

For the first time, scientists have cleanly corrected a human gene mutation in a patient’s stem cells. The result, reported in Nature last week, brings the possibility of personalised cell therapy for genetic disorders of the liver 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.

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 a mutation in a gene causing alpha1-antitrypsin deficiency. Using ‘molecular scissors’ to snip the genome at precisely the right place, they 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 corrected cells were then shown to be producing normal alpha1-antitrypsin protein.

Dr Ludovic Vallier, Medical Research Council senior Fellow and Principal Investigator at the University of Cambridge’s MRC Centre for Stem Cell Biology and Regenerative Medicine said “We still have major challenges to overcome before any clinical applications but we have now the tools necessary to advance toward this essential objective.”

For the full article from University of Cambridge Research News click here

Yusa K, Rashid ST, Strick-Marchand H, Varela I, Liu PQ, Paschon DE, Miranda E, Ordóñez A, Hannan NR, Rouhani FJ, Darche S, Alexander G, Marciniak SJ, Fusaki N, Hasegawa M, Holmes MC, Di Santo JP, Lomas DA, Bradley A, Vallier L: “Targeted gene correction of α(1)-antitrypsin deficiency in induced pluripotent stem cells.”  Nature. 2011 Oct 12. doi:10.1038/nature10424 link

 


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