A Bright Future: Breakthrough Gene Editing Trial Reverses Leukaemia

1 year old Layla Richards, recipient of the trial. Sharon Lees/ Great Ormond Street Hospital

A pioneering gene editing therapy has shown remarkable success in a unique trial at Great Ormond Street, paving the way for a wave of gene editing trials. 

A world first

Not long ago, 1 year old Layla Richards had an incurable form of leukaemia and the prognosis wasn’t looking good. After a determined search for a cure, Layla underwent an experimental therapy in which ‘designer’ immune cells were implanted that would destroy and replace her own ailing immune system. 

What did the treatment involve?

Cells were extracted from Layla and were then edited by a cutting enzyme called a TALEN and had a new gene inserted by viral delivery. TALENS are one of 3 main targeting techniques including zinc fingers and the famous CRISPR-Cas9. The combination therapy rendered the new cells immune to anti-cancer drugs and instructed them to attack the remaining immune system. Layla then had another bone marrow transplant to replenish her immune system; which would now be free of leukaemia if all went to plan.

“We’re in a wonderful place compared to where we were five months ago, but that doesn’t mean cure. The only way we will find out if this is a cure is by waiting that one or two years, but even having got this far from where we were is a major, major step”

The gene editing step is not intended to be a cure, as the patient still requires a suitable transplant, but it offers a crucial lifeline and eradicates a form of leukaemia once believed incurable. 

We’ve been here before, but is it different this time?

Gene therapy has had a turbulent history. In the 1990s the first trial went ahead to treat ‘bubble boy syndrome’, in which patients have no functional immune system. While some of the patients were seemingly ‘cured’, a couple also developed leukaemia after the treatment. This was a massive setback for the field, but it’s now beginning to recover. We’re now older, wiser, and know more about DNA. We know that some viruses will insert DNA in such a way that can cause cancer in certain conditions – but modern efforts have significantly reduced this risk. 

“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. I think we’re seeing the fruits of those early studies right now, so I think this is real”

The first gene editing trial on humans has been successful against HIV

HIV-1 virus particles budding (green)

This is a wonderful moment for the field and although it will take time to confirm actual success, it actually isn’t the first of its kind. Sangamo Biosciences in California have already tested a treatment using zing finger nucleases to tackle HIV. Results are looking promising; 70 patients have been treated so far and are indicating resistance to the virus. 

Are we looking at a bright future for gene editing? 

Yet again, it’s still uncertain. Things are looking better than ever before however, and many initial safety concerns have been addressed. In both treatments the editing happened in a laboratory with cells extracted from the patient’s body. This allows screening of cells to make certain you’ve created what you wanted.  There are however still concerns about direct treatments injected straight into the body, due to fears cutting enzymes may cut in other places too. Viruses are also still being perfected so that they don’t create an immune response.  With time and investment however, these could be corrected and improved – and we could be looking at a serious revolution. 

“I get goosebumps thinking about the potential of this technology” 

Read more at Nature and BBC News