Gene therapy before birth
Genome editing makes it possible to treat diseases of the embryo in the womb
Researchers from Carnegie Mellon University and Yale University for the first time applied a gene editing technique to experimental mice for the successful treatment of a genetic disease during fetal development of the embryo.
Every year, about eight million children are born with serious genetic disorders or birth defects. They can be determined during pregnancy, for example, with the help of amniocentesis – analysis of amniotic fluid, but there are no ways to correct harmful mutations before birth.
"At the beginning of embryonic development, there are many stem cells dividing rapidly. If we can correct the genetic mutation at this moment, we could significantly reduce the effect of the mutation on fetal development or even completely get rid of the disorder," says Professor Danith Ly from Carnegie Mellon University in a press release Gene Editing Technique Cures Genetic Disorder in Utero.
In the current study, peptide-nucleic acids were used for genome editing. These are synthetic molecules in which nitrogenous bases are attached to the protein molecular chain, capable of connecting according to the principle of complementarity with the nitrogenous bases of DNA and RNA. Specially designed in the laboratory, peptide-nucleic acids "target" a compound with a DNA site containing a certain mutation (in the current experiment, it was a mutation in the beta-globulin gene that causes beta-thalassemia disease). An already tested nanoparticle is used to deliver molecules to the embryo. By injection into the amniotic bladder, nanoparticles get to the embryo. They carry a peptide-nucleic acid molecule paired with a DNA strand. By attaching to the right place of DNA in the embryo cell, the peptide-nucleic acid unpacks the DNA double helix, and the donor DNA attaches to the defective site, triggering cellular DNA repair mechanisms that correct the mutation.
In an experiment, scientists managed to correct a mutation associated with beta-thalassemia in 6% of cells. A single injection of the drug was enough to significantly reduce the severity of the disease in the born mice, so much so that they can be considered cured. The hemoglobin level in the blood of these mice was within the normal range, the spleen was less enlarged, and their survival rate increased. It is assumed that the method will be even more effective if it is used several times during pregnancy. The researchers also note that this method has no side effects, unlike, for example, the CRISPR/Cas9 method, which can mistakenly damage other DNA sites. According to the scientists, they analyzed 50 million samples and found none where their method would have an impact outside the target area.
The results of the study are published in the journal Nature Communications (Ricciardi et al., In utero nanoparticle delivery for site-specific genome editing).
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