Layla Richard’s story is remarkable and a world first. On the day before her first birthday, Layla’s parents received the devastating news that her treatments were unsuccessful and her leukaemia was terminal. Now, just months later, Layla is not only alive, but also has no trace of leukemia in her body.
Layla’s parents refused to give up, and their determination led to her receiving an experimental treatment that had previously only been tested on mice. The treatment involved collecting white blood cells from a healthy donor and editing them. The cells were modified to recognise and kill leukemic cells, while also having their receptors removed to avoid damage to normal tissue. Finally, the cells had a surface molecule removed, making them ‘invisible’ to the strong drugs used in leukemia treatment, avoiding destruction.
Gene therapy techniques were first raved about at the beginning of the millennium, but little information or breakthroughs followed this. Professor Adrian Thrasher of Great Ormond Street Hospital said, “There was a lot of hype that was unrealistic at the time, the technologies were very new and it’s taken 15-20 years for those technologies to mature”.
He continued: “I think we’re seeing the fruits of those early studies right now, so I think this is real”.
Early work with gene therapies involved inserting new DNA into the cells of patients with missing or abnormal instructions in their genetic code. The most famous cases involved those with ‘bubble boy syndrome’, people who have no immune system due to a defect in a gene called IL2RG. A virus was used to ‘infect’ the cells with a healthy copy of the DNA; however, trials were stopped after patients developed leukaemia.
Since these early trials, more knowledge has allowed greater precision in techniques. Zinc fingers, Talens and Crispr are three key technologies used today. They act in a similar way to a satnav, finding their way to specific sites in the DNA. These new technologies have opened up a new field of genetic engineering in which new information can be inserted, as well as existing DNA instructions being rewritten.
In Layla’s treatment, Talens were used to engineer the donor’s white blood cells to avoid damage from cancer treatment and to prevent the cells from attacking healthy tissue. A virus was then used to insert a new gene, instructing it to attack leukaemia cells.
Professor Waseem Qasim, who was involved in Layla’s therapy said, “The technology is moving very fast, the ability to target very specific regions of the genome has suddenly become much more efficient.
“The technology itself has got enormous potential to correct other conditions where cells are engineered and given back to patients or to provide new properties to cells that allow them to be used in a way we can only imagine at the moment”.
Doctors are now hopeful that these techniques can be used to target not only cancer, but also a range of blood or immune system diseases and inherited disorders including beta thalassaemia and sickle cell anaemia.
Thrasher is predicting an “explosion” in genetic engineering over the next 10 years; it seems the dawn of gene-editing has finally arrived, 15 years after it’s original hype.