![]() Scientists at the laboratory of synthetic embryology at Rockefeller University, New York found that some aneuploid embryos can self-correct. What did the study into aneuploid embryos find? Mosaic embryos can have different proportions of normal and abnormal cells and there is a criterion ranging from low-level mosaic where 20 to 40% of the cells are abnormal to high-level mosaic. Data suggests that mosaic embryos account for up to 20% of all PGT-A-tested embryos. The term mosaic embryos were coined to describe embryos that have a mix of normal and abnormal cells. Previously, embryos were categorised as normal or abnormal, but in the mid-2010s, embryologists discovered that blastocysts aren’t necessarily 100% euploid or 100% aneuploid: sometimes they’re a mixture. This is performed to reduce the risk of miscarriage.Įmbryos with the correct number of chromosomes are called euploid and have a higher chance of leading to a successful pregnancy than those with the incorrect number of chromosomes or aneuploid embryos. Yet almost all inherited diseases can be prevented for most couples by existing forms of screening, such as testing IVF embryos before implantation, without any need for CRISPR.New research has found that mosaic embryos, currently ruled out for IVF selection, could self-correct and lead to healthy pregnancies.ĭuring embryo selection, a test known as preimplantation genetic testing for aneuploidy (PGT-A) is used to screen aneuploid embryos which have an incorrect number of chromosomes. A recent report by the US National Academy of Sciences concluded that trials of this kind of gene editing should be allowed only if they meet a number of criteria, the first being “the absence of reasonable alternatives”. An alternative would be to fix the DNA inside stem cells from would-be parents, and then use these to generate egg or sperm cells with repaired DNA.Įven if it does become possible to safely edit our children’s DNA, that doesn’t necessarily mean we should. This approach has already reduced mosaicism in monkey embryos. Injecting the CRISPR machinery into an embryo as soon as possible after fertilisation and then destroying it a few hours later should ensure repairs only take place before the DNA replicates. “This would need to be solved before the methods could be used clinically to correct a disease,” says Lovell-Badge. Similarly, tests to ensure there aren’t any unwanted or dangerous mutations elsewhere in the genome wouldn’t be reliable. Testing wouldn’t be able to tell for sure whether the mutation has been fixed. This is a big problem, as it means a child could still develop the disease that gene editing was supposed to prevent. So when they divided, some cells inherited unrepaired DNA. ![]() The team injected the CRISPR machinery when the embryos were just single cells, but it seems that, in these two embryos, it didn’t make repairs until after they had replicated their DNA. Two of the edited embryos were mosaics – mixtures of edited and unedited cells. However, the study highlights a further roadblock to using gene editing to create healthy babies. “It does look more promising than previous papers,” says Fredrik Lanner of the Karolinska Institute in Sweden. The team managed to correct mutations in three out of six embryos, suggesting CRISPR repair is more efficient in viable embryos. “Mosaicism would need to be solved before embryos can be gene edited to correct a disease” Mosaic of cells They used unwanted immature eggs donated by people undergoing IVF, matured them, and fertilised them with sperm from men with genetic diseases. Now a team at the Third Affiliated Hospital of Guangzhou Medical University in China has tried the technique in viable embryos ( Molecular Genetics and Genomics, doi.org/b35x). However, these embryos were genetically abnormal, formed from the fertilisation of an egg with two sperm, and would never have been able to give rise to a child. ![]() The first two attempts to fix genes in human embryos repaired very few embryos. IVF produces only a few embryos, and even fewer live births, so CRISPR must work most of the time if it is to be used during IVF. While CRISPR is very efficient at disabling genes, it is less good at repairing faulty ones – a more useful application when it comes to embryos. The second obstacle has been efficiency – the proportion of embryos fixed. The technique has been refined to make such “off-target” changes extremely rare, plus there are ways to check embryos for unwanted changes before implanting them into the womb. However, this is becoming less of a concern. As well as correcting a bad mutation, the CRISPR machinery can also make unwanted changes elsewhere in an embryo’s genome, which may lead to cancer. There have been two big obstacles to using the technique, however.
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