造血干细胞,CRISPR-Cas9基因编辑 z-bo 2020-09-30 384

　　In a new study, researchers at research institutions such as the Fred Hutchinson Cancer Research Center in the United States used CRISPR-Cas9 genes to edit long-lived hematopoietic stem cells, causing problems such as sickle cell disease and β-anemia. Was upside down. Clinical symptoms are observed in certain blood diseases. This is the first time that scientists have specifically edited the genetic makeup of a specific subgroup of adult hematopoietic stem cells, which are the source of all cells in the blood and immune system.

　　This proof-of-principle study shows that effective modification of targeted stem cells can reduce the cost of gene editing treatments for blood and other diseases, and reduce the risk of side effects. The corresponding author of this article, Hans Peter Kim, director of the Stem Cell and Gene Therapy Program at the Fred Hutchinson Cancer Research Center, said: Some diseases, such as cancer, use the same method.

　　Keem said: "For this subpopulation of hematopoietic stem cells, it is possible to help millions of patients with blood diseases. It may lead to human death. In the preclinical studies of clinical trials, these researchers chose sickle cell disease. Genes related to β-thalassemia. These genes are blood diseases caused by genetic defects in hemoglobin production. Other studies have shown that reactivation of fetal hemoglobin (a type of hemoglobin related to fetal development, but no longer produced on the first birthday ) Can reverse the symptoms of the disease.

　　These researchers used CRISPR-Cas9 gene editing to delete certain genetic codes that normally interfere with the production of fetal hemoglobin. Using CRISPR to cut this controlled DNA fragment, red blood cells can continuously produce high levels of fetal hemoglobin.

　　These researchers have effectively edited the target stem cells. Before injection, 78% of the target stem cells were edited in a laboratory dish. When these edited stem cells are injected into the body, they colonize the body, proliferate and produce blood cells. 30% of them contain the edited genetic code. It can bring fetal hemoglobin up to 20% of red blood cells, and can reverse the symptoms of sickle cell disease and hematuria.

　　Keem said: "We found that these stem cells can not only be effectively edited, but also colonized at a high level, so we are very looking forward to turning them into a very effective treatment for the human body."

　　Among these researchers, 20% of the red blood cells carry fetal hemoglobin-what is observed using this method-is sufficient to reverse the symptoms of sickle cell disease. We also believe that the genetic repair of the small cell population required for therapeutic effects can reduce safety Sexual issues and reduce the risk of off-target effects. Dr. Olivier Humbert, a researcher at Kiem Labs and the first author of this article, said: “Since CRISPR technology is still in its infancy, it is more important to prove that our method is safe. No harmful effects were found on the edited cells. This is an off-target mutation, and we are currently conducting long-term follow-up to ensure that no adverse reactions occur. "

　　This is the first specific compilation of a handful of hematopoietic stem cells discovered by the Kiem team in 2017. This is an investigation. Hematopoietic stem cells are fully involved in the regeneration of whole blood and the immune system. In order to distinguish, the Kiem group called this part of hematopoietic stem cells CD90 cells. It is named after the protein marker CD90 and allows CD90 cells and the rest of hematopoietic stem cells (carrying another protein marker: CD34). Discrimination. These self-renewal properties of stem cell populations are likely to be candidates for gene therapy, because they can produce these genetically modified blood cells for a long time and treat this disease for life. Given that they account for only 5% of all hematopoietic stem cells, targeting them with gene editing complexes will require less supply and potentially reduce costs.