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Gene-editing advance: implications for A-T

There has been a lot of media coverage over the last couple of days of the news that scientists in Oregon have for the first time managed to edit the DNA of a human embryo (effectively a fertilised egg) to remove a mutation which if left would give rise to a serious genetic condition. This means that potentially in future such an embryo could be implanted by IVF techniques into the mother and ultimately produce a child free from the condition. Scientists have been quoted as saying that they believe the same approach could work for other conditions caused by single gene mutations, such as cystic fibrosis and certain kinds of breast cancer. This has led to families contacting the A-T Society to ask whether this has positive implications for people living with A-T.

While this is undoubtedly a major achievement scientifically, and shows what can be achieved by the new technologies in terms of positively manipulating DNA, it doesn’t for now offer much that is new to families living with A-T.

The technique involves inserting Crispr-Cas9 enzyme into a fertilised egg to correct the mutated DNA. After this the egg can in theory be implanted into the mother using IVF techniques to produce a child free of the mutation

This is an advance on the currently-available technique of pre-implantation genetic diagnosis. This is a form of IVF where the fertilised eggs are genetically tested before they are implanted so that only those free of the mutation are used. The main advantage of the technique set out in the paper is that because it is potentially possible make each available embryo ‘mutation-free’, you would end up with more of them available for implantation.

However, the condition for which researchers have succeeded in doing this is one that is caused by a single ‘dominant’ copy of the mutation. In other words, a mutation is inherited from only one parent and so is present on only one of the two strands of DNA. This is different from A-T where there must be a mutation from both parents (i.e. one on each strand of DNA) for the condition to develop.

The Crispr-Cas9 technology used in the procedure, cuts the DNA at the mutation site and the mutated section is then repaired by copying the other ‘correct’ strand. However, while this approach seems to work well where one strand is unaffected, it is obviously going to be problematic for a condition like A-T, where it may well be that the section used as a template also contains a mutation.

In addition to this, the technique makes use of the body’s own DNA repair techniques to carry out this process, and as we know A-T is a condition which negatively affects the body’s ability to repair DNA. So it might well be that the process wouldn’t work or wouldn’t work reliably in someone with A-T.

Nevertheless, while this discovery may not be of immediate benefit to people living with A-T, it does mark a significant step forward in our understanding of how genes work in developing embryos and our ability to modify defective genes, all of which will be very valuable to our efforts to understand and find new treatments for A-T.

You can see the original paper here and an interesting editorial here.