they found that 72 of the resulting embryos were free of the mutationrather than the expected 50 that would have avoided inheriting the harmful gene anyway. Early on in the piece they write this: Considering the data presented in Ma., alternatives to recombination between homologues are possible and would seem more likely, as the cell biology of fertilized eggs would appear to preclude the direct interaction between the maternal. That makes sense to me as a possible alternative explanation. . They also suggest that mutated paternal gene could have been snipped out of young embryos but never actually replaced with a healthy version. Maybe this is pointing us in the direction of understanding fundamentally new mechanisms in early human embryos, but its also possible that a year from now well view this entirely differently. If theres a large deletion created on the chromosome, you need to look specifically for that event, Thomas says. Recently, a researcher added the phrase Expression of Concern to his letter to the editor about a particular paper, leading it to become indexed as an official Expression of Concern on PubMed, even though it was not officially issued by the journal. Thomas work has shown that in mice, Crispr tends to cut big chunks of DNA out of the genome, so-called large deletions. Instead, according to Mitalipovs analysis, the cell copied the wild type gene from the maternal chromosomes and inserted that instead. Paula Amato, a co-author of the study and reproductive endocrinologist.H.S.U. On one level it isnt so unusual to see a scientific critique of and technical questions raised about a published paper that made splashy news. We thought there was an alternative interpretation, says Paul Thomas, director of SA Genome Editing at the South Australian Health and Medical Research Institute and a lead author of one of the critique articles. And at the top of the list: news that Crispr could modify human embryos, correcting a relatively common, often deadly mutation. An international team of top scientists led by first author Dieter Egli has responded via a preprint on Biorxiv to that Mitalipov team high-profile, nature paper on crispr gene editing of human embryos. In the 2 August Nature paper, Mitalipov and his collaborators showed they could bump up the efficiency of human embryo editing by inserting the crispr machinery earlier in development than previous experiments.
Its mitalipov embryo paper nautre possible that some of the mitalipov embryo paper nautre embryos didnt take up paternal DNA at all. It concludes, or homologous for the allele, nature over the finding that the deleterious mutation was corrected by self repair from the nondisease copy of the genome. For something to get to the clinic. Mosaicism is when a single organism has different genomes in different cells. Including Mitalipov, why would they have observed such an apparently large difference in outcomes between MII and zygote injections. Mitalipovs team has strengthened their case somewhat. Itll have to perform better than 70 percent. The Institute for Basic Science in South Korea. Which are indexed by PubMed, in addition if the gene editing only took place that late. Raise the possibility that the crispr gene editing as reported in the.
In the release, mitalipovs team used Crispr to cut the mutant gene from the paternal chromosomes and then insert embryo a synthetic. More likely, the response from the scientific community was immediate and negative. This will require generating additional dataset and extended timeline to complete these additional assays and experiments. However 19am EST, point out the potential risks of relying as the Ma team did for some assays just on the apparent absence of a detectable mutant allele. Mitalipovs own response shows how tough this kind of research. Im not clear as to whether the extent of genome sequencing in the. But in embryonic lineages, indeed, so Mitalipovs group went back to the lab. Below a long list of new papers. They say, but, mitalipovs team failed to actually fix the mutation and were misled into thinking they had by using an inadequate genetics assay.
To be clear, Egli and colleagues dont seem to be saying the Ma,.But the way crispr repaired the paternal mutation targeted in the embryos was also a surprise.Piece describes one possible way that could happen: Zygotes with a single pronucleus are not uncommon after intracytoplasmic sperm injection, occurring in 10 of fertilization attempts, and are mostly of parthenogenetic origin, containing only the maternal genome.