First human embryos genetically modified – more will come
The prospect of genetically engineering humans has come a step closer, with the publication of the first paper to describe efforts to modify embryos. There is a long way to go before we can safely tinker with our genes, but at least one group in the US and four in China are aiming to edit human embryos: this will be the first of many studies.
The work was done using a gene editing technique called CRISPR (pronounced “crisper”).
The idea of gene editing is to make specific changes in a particular gene, just as you might correct a spelling mistake. Gene editing has been around for decades, but in organisms other than mice it used to be difficult, expensive and time-consuming.
The CRISPR method – the name refers to characteristic sets of repeating chunks of DNA known as “clustered regularly interspaced short palindromic repeats” – developed in just the past few years, has changed all that, allowing biologists to achieve in weeks what used to take years.
The ease, speed and cheapness of CRISPR has made it possible for more people to experiment with gene editing. Last month, it was reported that a handful of teams are trying to modify human embryos using the method. Now one of those teams, led by Junjiu Huang at the Sun Yat-sen University in Guangzhou, China, has published its results.
Rejected eggs
“Because ethical concerns preclude studies of gene editing in normal embryos,” the team writes, the researchers used human eggs that had been fertilised by two sperm rather than one.
These “polyspermic” eggs may develop for a few days but never develop normally and are discarded by fertility clinics.
Huang’s team then attempted to modify one of the genes coding for the oxygen-carrying blood protein haemoglobin. Mutations in this gene cause the disease beta-thalassemia, itself a target for previous gene-editing attempts. The team injected the various snippets of RNA and DNA needed for CRISPR into the polyspermic eggs. One of the DNA sequences was a “template” for the desired changes to the gene, intended to guide the repair process.
Of the 86 eggs injected, just four were successfully modified – an efficiency rate far lower than required to make human germline gene editing a practical prospect. The others either did not survive, or were not successfully modified.
Missing the target
There were also changes to genes other than the globin gene. Such “off-target” alterations are a big concern, because they could cause serious illnesses.
It should be possible to reduce the number of off-target changes by refining the CRISPR method. However, it will probably never be possible to completely eliminate them. So if gene editing were ever to be used for modifying inherited human genetic material, it would be essential to check embryos for any off-target effects before implanting them in the mother-to-be.
In theory, this can be done by removing a single cell from a developing embryo and sequencing its DNA – a method already sometimes used during IVF to ensure embryos don’t carry serious disease mutations, called preimplantation genetic diagnosis.
Living mosaics
However, Huang and his colleagues found what could be a serious problem: the embryos were a mixture of modified and unmodified cells – so-called genetic mosaics. That means the results of preimplantation genetic testing could be misleading.
On the face of it, these findings are not encouraging for those hoping to use gene editing to correct hereditary diseases in children. However it is too soon to draw sweeping conclusions. The low efficiency and the mosaicism could be a result of using flawed eggs. There might also be a specific problem with their approach – the paper was published just a day after being received by the journal, so it has not yet been thoroughly scrutinised by independent researchers. What’s more, CRISPR is still a new method, so it is likely to be improved greatly in the coming years.
But should this kind of research be done at all? That depends on whether you think modifying the inheritable DNA of the human germline is acceptable. Some have called for a moratorium on this kind of work, and according to Huang, the paper was rejected by the journals Science and Nature in part because of ethical concerns.
Polls in various countries, however, indicate that there is actually substantial public support – sometimes over 50 per cent – for using germline modification to prevent genetic diseases.
The efficiency of gene editing can vary greatly across both species and cell types. So to find out whether any method is safe and effective it is necessary to try it in human embryos.
Journal reference: Protein Cell, DOI: 10.1007/s13238-015-0153-5
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