Molecular biologists for the first time managed to fix a dangerous mutation in the DNA of the embryo inside the womb of the mother, preventing the impending death of the mice due to the destruction of the liver in the first few days of life. Their findings and the results of experiments were presented in the journal Nature Medicine.
“Our main task is to adapt these laboratory tools to fight real diseases in the diagnosis of pregnant women. We hope that our approach will give physicians the ability to deal with mutations that either kill the child or cause severe problems after birth,” said William Perento (William Peranteau) from the University of Pennsylvania in Philadelphia (USA).
Genomic editor CRISPR/Cas9, named chief scientific breakthrough 2015, was created by American scientist Feng Zhang (Feng Zhang) and several other molecular biologists about three years ago, and since then it has undergone several upgrades that allow scientists to use it to edit the genome with absolute precision.
In fact, CRISPR/Cas9, like many other things, not invented people, and nature — initially, this system is developed inside bacteria hundreds of millions of years ago to protect against retroviruses. It consists of two components — a “library” of samples of the genetic code of viruses (CRISPR) and Cas9 enzyme, looking for similar sequences in the bacterial DNA and removing them if necessary.
A year ago, scientists crossed an important boundary – they conducted the first experiments on human embryos with CRISPR/Cas9. Disabling one of the critical genes, genetics followed what functions it performs in the cells of the embryo and how it can be associated with the development of infertility.
Successful implementation of these experiments, as noted Perento, opened to scientists the ability to use CRISPR/Cas9 or other genome editors to remove potentially fatal mutations from the genomes of embryonic cells and the protection of children from congenital diseases.
Perento and his colleagues conducted the first experiment of this kind, attempting to remove malicious mutation in the FAH gene from the DNA of mouse embryos that developed in utero in pregnant mice.
Damage to this gene leads to the development of tyrosinemia – inability to break down the molecules of tyrosine, one of the most important amino acids. Its accumulation in the body causes cells in the liver begins to appear fumarylacetoacetate, an extremely toxic substance, causing their mass death. As a rule, carriers of mutations in the FAH die in the first days or months after birth, if they don’t start to take substances, neutralizing tyrosine and related toxins.
To combat such mistakes, the researchers used not one, but two genomic editor is already mentioned CRISPR/Cas9 and more accurate, but indiscriminate BE3 enzyme that transforms one type of “letters” of DNA to another.
As planned by scientists, first plays the role of “guide” that helps the protein to find “typos” within FAH and a point to fix them without adding new mutations that sometimes appear when cutting DNA full version CRISPR/Cas9.
Using such a “hybrid” editor, inserted in a retrovirus, scientists have successfully “fixed” FAH in most cells in embryos and raised healthy pups, not needing constant medication. Their liver is about 60% consisted of hepatocytes with a normal version of this gene, and in General they looked more healthy than their relatives, taking these drugs.
Now geneticists are working to create “disease-free” variants of this gene therapy, and think about its application to combat other genetic diseases caused by single “typos” in the DNA.