Source: Yale University
Summary: Researchers conducted the first demonstration of site-specific gene editing in a fetus, correcting a mutation that causes a severe form of anemia.
For the study, this gene-editing package was injected into the fetuses of mice. At four months after birth, the mice had been cured of thalassemia, an inherited defect in oxygen-carrying red blood cells. The technique involves an intravenous injection of nanoparticles carrying a combination of donor DNA and synthetic molecules known as peptide nucleic acids (PNAs). The PNAs, which mimic DNA, bind to the target gene and form a triple helix an aberration that triggers the cells’ repair mechanisms. As part of this process, the healthy donor DNA paired with the PNA in a nanoparticle is used to fix the mutation. The study findings were published in the journal Nature Communications.
Using nanoparticles for delivery is crucial, said the researchers. When injected intravenously without nanoparticles, PNAs are cleared from circulation within about 30 minutes. When delivered by a nanoparticle and taken up by a cell, though, they remain much longer. The research team made the nanoparticles with a degradable polymer and designed them small enough, 200 to 300 nanometers to readily accumulate in the liver of the fetus, where the stem cells are located before migrating to the bone marrow. By editing the gene in the fetus for the new study, though, the researchers greatly minimized the amount of damage caused by the disease.
Prof. Peter M. Glazer said, “The treated mice had normal blood counts, their spleens returned to normal size, and they lived a normal lifespan – whereas, the untreated ones died much earlier.”
More Information: Adele S. Ricciardi et al, “In utero nanoparticle delivery for site-specific genome editing”, Nature Communications (2018). DOI: 10.1038/s41467-018-04894-2