US biotech firm Sangamo Therapeutics used genome editing to introduce a working copy of a faulty gene into patients with a rare inherited disorder, Hunter syndrome. In two patients, the gene was successfully introduced into the DNA of target liver cells, and it did not cause adverse effects. However, it had no effect on symptoms.
Hunter syndrome is caused by mutations in the IDS gene, which codes for the enzyme IDS, also known as I2S, which metabolises carbohydrates known as glycosaminoglycans (GAGs). With the body unable to process GAGs, toxic by-products slowly build up, leading to progressive and widespread organ damage.
The standard treatment involves weekly infusions of the missing enzyme. Seeking a permanent cure, the researchers used zinc finger nucleases in a viral vector to deliver a functioning copy of the IDS gene to the patient's liver cells, spliced specifically into an active region of the genome (see BioNews 927).
Similar approaches have been used on cultured cells, but this is the first time the technique has been successfully deployed in the bodies of human patients. In contrast to the recent controversy over the Chinese scientist Dr He Jiankui – who claimed to have edited genes in embryos (see BioNews 977) – the DNA alterations do not pass down to future generations.
Sangamo presented their results to the WORLDSymposium conference on 7 February 2019. Liver biopsies confirmed that the IDS gene had been introduced into two patients' genomes, but levels of IDS enzyme in blood and GAG breakdown products in urine were unchanged. One patient did show increased IDS activity, but the response was short-lived – and may have been caused by an immune response to the viral delivery mechanism used to transport the genome editing components into cells.
Reaction to the news was mixed. Share prices for Sangamo fell significantly, suggesting that investor expectations may have got ahead of the technology.
However, Dr Tyler Reimschisel of Vanderbilt University, Tennessee – who was not involved with the study – said: 'It's not discouraging, it's just early and on a small amount of people… This is definitely a novel and innovative treatment.'
The company also released data for a similar trial on Hurler syndrome – a related metabolic condition caused by a different gene. This trial is at an earlier stage, and although no adverse effects have been detected, it is too early to say if the treatment has been effective.