Researchers at the Washington University School of Pharmacy used improved gene therapy to enable healthy mice and dogs with Haemophilia A to survive. The gene therapy method is to introduce a gene into animal cells. This gene encodes a blood coagulation factor called coagulation factor VIII (it cannot be coded for in the gene loss of an animal with hemophilia). ). The results of this study will be announced on Proceedings of the National Academy of Sciences. Hemophilia is a genetically prone to hemorrhagic disease, which is caused by an inherited mutation in the X chromosome blocking the production of normal coagulation factors, which are X-linked recessively inherited. Hemophilia greatly limits the daily life of the patients. When they are bleeding by trauma, the wounds cannot heal automatically; even if running, joint hemorrhage occurs. In addition, after a long time, patients suffer severe consequences from joint damage and a series of complications due to excessive bleeding. Due to the large gene encoding factor VIII, it is difficult to use a suitable gene vector, so the gene therapy of hemophilia A is greatly limited. Therefore, the researchers removed a portion of Factor VIII genes and other genetic components, thereby minimizing the transduced genes, while also using a large gamma retroviral vector. After the carrier containing the factor VIII gene was injected into the blood of hemophilia A-born mice and puppies, blood tests showed that all animals were able to produce factor VIII, and in blood clotting tests, clotting factors The coagulation activity of VIII is high. "This result made us very excited," said researcher Ponder who has published this gene therapy (Associate Professor of Pharmacy, Biochemistry, and Molecular Biophysics at the University of Washington): "Because I have treated with this improved genetic technology Dogs with hemophilia A have a 20-fold increase in the number of factor VIII produced in their bodies and a high level of factor activity, which has never been seen before, especially in large animals." Researchers use newborn animals There are two reasons for conducting the study: First, they are in the growth stage. The new cells that have been expanded during the growth process by the living cells that have been integrated with the genes all have genes that encode clotting factors, and their functions include clotting factors as they grow. Gene cells will increase many times. Second, the immune response in mature animals inhibits and reduces the activity of clotting factors. However, the immune system of primary mice and puppies is not mature, which reduces the possibility of intracellular resistance to the immune response into the gene. Obviously, the ultimate goal of the research is to apply this gene therapy technology to humans, but humans have a more mature immune system than mice at birth, so Ponder thinks, “When this technology is applied to animals that are closer to humans At that time, there may be a greater immunosuppressive response, so the next step is to experiment with this gene therapy in primates to see if there are ways to stop the immunosuppression (intern reporter Su Guohua). //)"
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