Patients in Europe are going to be offered a revolutionary gene-splicing therapy this year for the first time. The treatment, which has now received regulatory approval and which is being offered by the biotech company CRISPR Therapeutics, is aimed at curing a blood disorder known as β-Thalassaemia by correcting the genetic mutation responsible for the condition. This will be the first time that humans are treated with this technology in the Western world.

Β-Thalassaemia is a blood condition that negatively impacts the production of haemoglobin, limiting the patient’s ability to transport oxygen. This can lead to oxygen deprivation around the body, which over time can cause slower or stunted growth, bone deformities, fatigue, and shortness of breath. The disease is genetically simple, being characterised by a single mutation in the HBB gene; this simplicity has made it an attractive target for gene editing therapies.

One of the groups hoping to exploit our understanding of the HBB gene is CRISPR Therapeutics, which wants to use the gene editing technique CRISPR to permanently correct the mutation. The trial will be using ex vivo haematopoietic stem cells from patients, which can be edited under in vitro conditions in the lab. Once the editing has been completed, the ‘cured’ stem cells can be returned to the patient, where they should develop into healthy blood cells.

“Assuming they do get going, we will look back and think that this is the real beginning of gene therapy,” said Robin Lovell-Badge, PhD, Group Leader and Head of Steam Cell Biology and Developmental Genetics at the Francis Crick Institute in London. “It will obviously be critical to check that there are few and hopefully no problems with the new methods, but as far as I know, the preclinical trials look very promising.”

The treatment hopes to silence genes that are involved in the repression of foetal haemoglobin production pathways. In adults, these pathways are suppressed by the BCL11A gene while other production networks, including the HBB gene, take over haemoglobin production. If successful, this therapy would prevent the silencing of the foetal pathways and patients would see a substantial increase in healthy haemoglobin production.

“Certainly, 2018 promises to be the big year for clinical trials using CRISPR based genome editing,” said Helen O’Neill, PhD, a Molecular Geneticist involved in Embryology, IVF, and Reproductive Genetics at University College London. “Results presented by [CRISPR Therapeutics] at a haematology meeting showed that the method dramatically increased foetal haemoglobin in β-Thalassemia patients’ cells. The therapy successfully edited over 90% of blood stem cells removed from patients, which were retransfused.”

CRISPR Therapeutics is not the only company looking to attempt this type of treatment. Intellia Therapeutics and Novartis recently announced a partnership to work on a similar approach, while Sangamo Therapeutics is looking to expand their Zinc Finger Nuclease treatment trials to β-Thalassaemia in collaboration with Bioverativ.

There are still some concerns within the gene editing community that CRISPR could be harmful for patients by generating a large number of unintended, undesired mutations within the genome. However, gradual improvements in the CRISPR system have significantly improved the technique’s accuracy and specificity, suggesting that the tool may be suitable for clinical use. In China, where regulations on gene editing are less tightly controlled, there are already several CRISPR clinical trials underway.