The transplantation of a chromosome into the cells that have a genetic defect is proving to be a valuable solution to combat various genomic diseases, such as chronic granulomatous or Duchenne dystrophy. A team of researchers from Humanitas and the Institute for Genetic and Biomedical Research (CNR-Irgb) have identified this new method that eliminates numerous DNA alterations. Their work has also been published in Stem Cells, one of the most authoritative scientific journals.
The study by Humanitas and Cnr-Irgb
Unfortunately, not all hereditary diseases can be cured by a chromosome transplant, since some of them are due to large genomic alterations such as aneuploidy, duplications, inversions and other complex rearrangements, which do not allow for a targeted intervention. For all those that allow it, instead, researchers at the Institute of Genetic and Biomedical Research (CNR-Irgb) and Humanitas have developed a new method that could allow you to treat these diseases. The new approaches to gene therapy for hereditary diseases, based on CRISPR/Cas9 technology and on the use of special viral vectors that have greatly simplified the correction of small genetic alterations, are based on the idea of transplanting an entire chromosome into the cells with the genetic defect. As Marianna Paulis of CNR-Irgb explained, “the principle is that replacing the entire chromosome eliminates numerous genomic alterations that are currently incurable. A chromosomal transplant is precisely the replacement of the altered chromosome with that of a healthy donor: in this way the genome of the cell returns perfectly normal.
New perspectives
While until now it was possible to transfer a whole chromosome from one cell to another, but it was believed that it was not possible to eliminate the damaged chromosome at the same time, after a long trial it was shown that the new approach is able to cure in a test tube cells of a severe immunodeficiency such as Chronic Granulomatous Disease, in which some blood cells are not able to eliminate infections. “Now we have reprogrammed the cells of the patient of this disease by obtaining pluripotent stem cells capable of differentiating themselves towards any type of tissue, and in particular in those that have the functional defect – explained the researchers -. The cells that have been reset were corrected by chromosomal transplantation and then differentiated into cells of the immune system (granulocytes) which are those that are not working in this disease. These cells have acquired the new healthy chromosome with the simultaneous elimination of the damaged chromosome. It was thus demonstrated that the correct cells had regained the ability to eliminate pathogenic bacteria, which is equivalent to having potentially cured the disease. The next step researchers are working on is to transfer the method of chromosome transplantation into human cells. There are many diseases that could benefit from this approach, first of all the Duchenne Dystrophy, a serious muscular disease”.
