Study uses genome editing inside patient for first time

A new clinical trial in California marks the first time that genome editing has been used inside the body, rather than on cells such as blood or skin which can be extracted, edited outside the body, and then replaced.

A patient with the metabolic disorder Hunter syndrome was given an infusion containing a type of genome editing machinery called zinc finger nucleases as well as billions of DNA copies of the gene which codes for a protein they lack.

The treatment targets the liver cells. 'We cut your DNA, open it up, insert a gene, stitch it back up,' said Dr Sandy Macrae, president of Sangamo Therapeutics, which is running the trial. 'It becomes part of your DNA and is there for the rest of your life.'

People with Hunter syndrome lack a working copy of the gene that makes a protein called albumin. Without this enzyme, the body cannot break down complex sugars called mucopolysaccharides and so these molecules accumulate in the body's cells causing damage to the brain and many other organs.

The one-off treatment will not reverse damage already caused, but if successful will replace weekly intravenous infusions of the enzyme which can ease symptoms but do not prevent brain damage. Dr Paul Harmatz, leading the study at UCSF Benioff Children's Hospital in Oakland, California estimates that only one percent of liver cells need to be successfully edited for the patient to make an adequate quantity of the enzyme.

The therapy is being tested in adults, but if proved safe and effective will hopefully be available to child patients in future. By providing the treatment early in life it is hoped that the mucopolysaccharides will build-up and subsequent tissue damage can be minimised or avoided altogether.

The first recipient of the treatment was Brian Madeux from Arizona. He has had 26 surgeries so far in his life as a result of Hunter Syndrome, and says he took part in the trial because he is 'in pain every second of the day'.

'I'm willing to take that risk,' he told the Associated Press. 'Hopefully it will help me and other people.'

It will take about three months before tests show whether the treatment has been successful. 'I'm nervous and excited,' said Madeux. 'I've been waiting for this my whole life, something that can potentially cure me.'

'There's a lot of potential for treating liver diseases in this way,' said Professor Robin Lovell-Badge at the Francis Crick Institute in London, not involved in the trial. But he warned that the approach may not be applicable to other types of conditions: 'Taking it to more complex things like muscular dystrophy and cystic fibrosis will require a lot more work.'

The latest developments in genome editing will be discussed at the session 'What Next for Genome Editing? Politics and the Public', at the Progress Educational Trust's upcoming public conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction'.

The conference is taking place in London on Friday 8 December 2017. Full details - including sessions, speakers and how to book your place - can be found here.