Was fatal disease cured in human embryos? After all it seems it wasn’t

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The study, in which a team of scientists claimed to have corrected for the first time a hereditary and fatal mutation in human embryos through CRISPR – a genetic engineering tool – has now been called into question by well-known stem cell and genetics researchers.

According to the article published by these same researchers in the journal bioRxiv, there is no biological mechanism that explains how a genetic mutation in the sperm can be overcome using the version of the same gene transported in the ovule. The researchers go even further and claim that the team, led by Shoukhrat Mitalipov, “could never really fix the genetic mutation”, and that “they were led to believe that they had done so because they used an adequate genetic test”.

About a month ago, an international team of scientists led by Shoukhrat Mitalipov, a biologist known for creating stem cells based on skin cells, has announced that he has cured human embryos with hypertrophic cardiomyopathy after repairing a very common mutation that causes this hereditary and fatal disease. Since this disease is caused by an error in the information carried in the MYBPC3 gene, the scientists used CRISPR to eliminate the wrong genetic information and paste a correct version.

In this study published in the journal Nature, Mitalipov explained how he would have achieved such a feat. What the scientists did was inject into the donated eggs by healthy women the spermatozoa of a sick man and at the same time the CRISPR. This editing tool led RNA guides, a DNA-like acid responsible for cell protein synthesis, whose function was to find the exact location where genes need to be corrected. It also carried enzymes, which functioned as scissors that would cut the defective part of the DNA. When this part was cut, the correct information stored in CRISPR was pasted into the DNA and the genetic material was completely correct.

Of the 58 embryos that resulted from this pioneering in vitro fertilization, 42 were completely free of the mutation of the gene that caused hypertrophic cardiomyopathy, so Mitalipov announced a 72% success in this technique. However, according to the study led by Dieter Egli, a stem cell scientist at Columbia University, and by Maria Jasin, a development biologist at the Sloan Kettering Oncology Center, there is reason to believe none of this has happened.

Egli presented two explanations that show how Mitalipov may have misinterpreted the results of the experiment. The first explanation says that after fertilization, the genetic material of the sperm and egg are separated at opposite ends and separated by a membrane for a few hours. This would make it very difficult for CRISPR to cut the wrong mutation of one part and get the right genetic information from the other party in a process called “homologous recombination”.

According to Dieter Egli and Maria Jasin, this process may not have been detected by Mitalipov’s team because they may have used a genetic assay that concealed another mechanism, CRISPR may have simply cut genetic information from the parent without ever replacing that material with other. To correct the gap, CRISPR may have “stitched” the ends of the DNA that were loose by joining random pieces.

The second explanation given by Dieter Egli and Maria Jasin states that there may have been a phenomenon called parthenogenesis, which occurs when a living being develops without the participation of the genetic information of a male and a female, but only of the female.

When questioned by Nature, Mitalipov says that “the study signed by Egli does not add anything new, it only offers alternative explanations for our results based on pure speculation”.

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