the modification of the embryo genome comes up against technical obstacles

the modification of the embryo genome comes up against technical obstacles

An embryo receives a dose of Cas9 protein under a microscope, in a laboratory of scientist He Jiankui's team, in Shenzhen, China, October 9, 2018.

A decade after hitting the labs, the Crispr-Cas9 genome-editing tool is still fueling a scientific and medical revolution and continues to raise unfathomable ethical questions. Evidenced by the 3e International Summit on Human Genome Editing, which was held in London, from March 6 to 9. It was an opportunity to hear the moving testimony of the American Victoria Gray, the first patient to have benefited from gene therapy for sickle cell disease. And to come back to the debates raised during the first two summits.

At the end of 2015, in Washington, the work of a Chinese team had agitated the scientific community. They had carried out an experiment on human embryos aimed at modifying the gene responsible for beta-thalassemia, a form of anemia of genetic origin. Crispr-Cas9’s sometimes described as “surgical” precision had been faulted, the tool modifying only a small proportion of the embryos, and inducing undesirable “off-target” modifications – the embryos in question were not intended to result in pregnancy.

In November 2018, in Hong Kong, the second summit was the scene of a resounding scandal, with the announcement, the day before its opening, by the Chinese biologist He Jiankui, of the very recent birth of twin girls whose genetic heritage had been modified with Crispr-Cas9 to give them resistance to HIV infection. International outcry! He Jiankiu, sentenced to three years in prison by the Chinese authorities, was released in April 2022. His first public speech, in February 2023, was a non-event, the scientist refusing to discuss his work or his fate. of Lulu and Nana, the two little girls.

Read also: Birth of ‘Crispr babies’ sparks universal condemnation

During the summit in London, there was no scandal, but a deepening of questions on the latest therapeutic advances – feasibility, cost, financing… – and on equitable access for patients. On the ethical level, the modification of gametes and embryos, which open the transmission of these characteristics to the next generation, fuels fears of eugenics and remains at the heart of debates.

Unwanted changes

For the time being banned in the vast majority of countries – including France, under the Oviedo Convention – the advent of the “baby-Crispr”, expected or feared depending on the philosophical options of each, comes up against technical pitfalls still unavoidable. This was recalled by several major figures in the field, including Shoukhrat Mitalipov (University of Oregon). His team has, in fact, published In NatureCommunicationson March 7, a study showing that DNA amplification techniques intended to ensure that a genetic modification has indeed taken place in an embryo can induce misleading artifacts: “It is unclear whether the expected deletion [perte d’un fragment d’ADN] is real or not”, he explained. Moreover, his analyzes suggest that genome editing of embryos can be accompanied by undesirable and deleterious modifications of their DNA around the target targeted by Crispr-Cas9.

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