Embryos protected from HIV
Russian biologists have created HIV-resistant human embryos
Daria Spasskaya, N+1
Scientists from several Moscow institutes conducted the first experiment in Russia on editing human zygotes using the CRISPR-Cas9 system and obtained embryos carrying a mutation in the CCR5 gene, which determines resistance to infection with the human immunodeficiency virus. The results of the study are described in the Pirogov RNIMU's own scientific journal – Bulletin of the Russian State Medical University (Kodyleva et al., The effectiveness of creating CCR5Ddelta32 deletion by CRISPR-Cas9 in human embryos).
The immunodeficiency virus infects cells, namely CD4+ lymphocytes, through interaction with a receptor on their surface, which is encoded by the CCR5 gene. A small part of the human population has a mutation in this gene (deletion of 32 nucleotides, CCR5Δ32), which blocks the interaction of the virus with the receptor and makes its carrier resistant to infection.
The idea to use this mutation for therapeutic purposes appeared after the story of the "Berlin patient", when a person with HIV, who received a bone marrow transplant from a donor with a mutation, was cured of infection. Genome editing tools developed since then (zinc finger nucleases and CRISPR-Cas9) They allow quite effectively to "turn off" CCR5 in lymphocytes, and HIV therapy methods using the patient's own edited lymphocytes are already undergoing clinical trials.
In 2015, Chinese scientists for the first time conducted an experiment on editing human embryos using the CRISPR-Cas9 system, and in 2016, the Chinese tried to introduce the CCR5Δ32 mutation into embryos. The editing efficiency in this experiment was only five percent (one embryo out of 20 contained the desired mutation).
Scientists from the Kulakov Research Center for Obstetrics, Gynecology and Perinatology, Moscow State University and Pirogov Medical University repeated the experiment of their Chinese colleagues, but modified the experimental conditions and obtained blastocysts homozygous for the desired mutation (that is, containing it in all copies of the gene) in 62 percent of cases.
As in the previous experiment, the scientists worked with defective trypronuclear (carrying three sets of chromosomes) zygotes (fertilized eggs) obtained as a result of artificial insemination and unsuitable for further implantation to mothers. The zygotes were injected not with Cas9 matrix RNA, but with a ready-made Cas9 protein complex with an RNA seed (guide RNA) and a DNA matrix to introduce the desired mutation. A pair of the most effective guide RNAs were selected in advance in an in vitro editing experiment. Of the 16 zygotes injected with the complex, 8 developed "in vitro" to the blastocyst stage (about 250 cells), after which they were used for genotyping. The analysis showed that five out of eight embryos contain the desired mutation.
In the long term, such editing of embryos may help to avoid infection, for example, for children of HIV-infected mothers.
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