For the first time, researchers have successfully used gene therapy to cure a genetic disease present in mice, paving the way for research into the treatment of genetic diseases in human fetuses.
Research on gene therapy continues to advance. While researchers have already been able to restore vision to visually impaired mice, they may soon be able to cure genetic diseases of children even before they are born. Indeed, researchers at Carnegie Mellon and Yale universities have used gene therapy to cure a genetic disease in a mouse model. Their work was published in the journal Nature Communications.
Every year, about 8 million children are born with serious genetic disorders or congenital malformations. Detected during pregnancy through amniocentesis, these genetic conditions cannot be corrected until birth. “At the beginning of embryonic development, there are many stem cells that divide rapidly: if we can correct an early genetic mutation, we could significantly reduce the impact of the mutation on the development of the fetus or even cure the disease,” says Danith Ly, a professor of chemistry at Carnegie Mellon’s Mellon College of Science.
To carry out their work, the researchers tested gene therapy on peptide nucleic acids (PNA), synthetic molecules with bases similar to DNA, but which differ in their skeleton. These peptide nucleic acids had previously been used to treat beta-thalassemia, a genetic disorder in blood leading to a reduction in hemoglobin production in adult mice.
The researcher’s technique uses a nanoparticle to deliver PNA molecules paired with the donor’s DNA at the site of a genetic mutation. When the DNA-ANP complex identifies a mutation, the APN molecule binds to the DNA and “unzips” its two strands. The donor’s DNA then binds to the defective DNA and stimulates the DNA repair pathways of the cell, allowing it to correct the error.
The researchers conducted their experiment on mice: they injected the ANP complex into the amniotic fluid of mice whose fetuses carried a mutation in the beta globin gene responsible for beta-thalassemia – thus using a technique similar to that of amniocentesis.
With a single injection of ANP during gestation, the researchers were able to correct 6% of the mutations: a great advance, since this correction caused significant improvements in the symptoms of beta-thalassemia in mice, including an increase in hemoglobin, spleen development and increased survival rate.
Unlike the CRISPR-Cas9 genome editing technique, which can damage DNA, the researchers noted that this ANP technique did not show off-target effects of treatment. “The ANP technique is ideal for therapy, it does not cut DNA, it fixes itself on it and repairs things that seem unusual. We looked at 50 million samples and found no off-site error”, says Professor Ly, who intends to continue his work. In particular, he wishes to know whether using this gene therapy treatment several times during gestation will enable him to achieve even higher success rates.