In the news

Use zinc finger nucleases (ZFNs) to direct highly specific insertion of a gene into DNA (a process called genome editing) to create effective treatment of a genetic disease in mice. 

A ‘humanised’ mouse model of the genetic disorder haemophilia B was created; these mice had no murine clotting factor IX gene, and only a mutated form of the human gene (hF9). ZFNs designed to target the hF9 gene sequence were joined to a healthy form of the hF9 gene to create a gene therapy vector that was injected into the mice. 

Liver samples from the mice removed after 10 weeks showed that the healthy hF9 gene had been successfully inserted in 1-3% of cells. Those mice that had received the gene showed human Factor IX levels of 2-3% in the blood and partially restored blood clotting amounting to effective treatment of haemophilia. 

ZFNs delivered with an appropriately designed gene-targeting vector can produce gene replacement at a specific position resulting in clinically significant correction of abnormal blood clotting caused by the faulty hF9 gene. Genome editing may therefore be ‘a viable strategy for the treatment of genetic disease’. 

One of the major problems with gene therapy is inserting the healthy gene only into the desired  place in the genome, since insertion in other places can disrupt other genes and effectively drive the development of cancer. This phenomenon, known as insertional mutagenesis, has previously caused leukaemia in gene therapy recipients (see previous news). It appears that ZFNs might offer a way of achieving much more specific (and hence safer) insertion of corrective genes; if borne out by further experiments, genome editing could indeed be an exciting advance for gene therapy.