Biology Report: X-linked severe complex immunodeficiency disease (XSCID) is a dangerous life-threatening genetic disease that can make the body's immune system paralyzed. So far, the only widely recognized gene therapy in the world is the treatment of this disease. Unfortunately, there have been reports that this gene therapy has major defects that may increase the risk of cancer in XSCID patients undergoing treatment. risks of.
Now, researchers from the University of Pennsylvania College of Veterinary Medicine and the American Institute of Allergy and Infectious Diseases have used living gene therapy to successfully restore the immune system of the bass pups with XSCID. They injected the puppy with a retrovirus containing a correct version of the XSCID gene. The results of this study were published in Blood magazine on April 15.
In humans, the XSCID affects one hundred thousandth of boys, who inherit the wrong version of a gene from the mother's X chromosome. Usually, this will be inherited and cause the child to die when he is born. This disease first caught public attention in the late 1970s when "Bubble Boy" David Vetter appeared: "Bubble Boy" David Vetter lives in a sterile environment throughout his life to protect him from Vetter died in 1984 after being infected by the outside bacteria.
The only treatment for XSCID is the replacement of hematopoietic stem cells that can continuously update immune cells by transplanting bone marrow from normal donors. Gene therapy using the normal genes in normal parental cells to replace defective genes to treat the disease has successfully cured 10 out of 11 boys in a French experiment in 1999. At that time, an in vitro method was used. The bone marrow cells of the affected boy were taken out of the body and incubated with a retrovirus vector containing a normal gene for 5 days, and then transplanted to the patient. What was wrong was that three boys developed T-cell leukemia, and the gene therapy trial was forced to stop.
Although in vitro gene therapy can restore the immune system function of XSCID boys, there are several problems. First, the number of bone marrow stem cells that can correct the gene in the patient's body is very limited in correcting this genetic defect. In addition, the in vitro manipulation and culture of cells can alter their ability to produce new immune cells over time.
In this new study, researchers in Pennsylvania used a different approach: direct injection of the retrovirus containing the correct gene into the blood vessels of XSCID puppies in the hope of correcting defective hematopoietic stem cells in patients. . The results showed that this therapy completely restored the immune function of three of the four treated puppies. The fourth puppy received the lowest dose of retroviral vector, so researchers believe that the effect of this treatment is a lower limit dose.
Since the boy who received the French gene therapy trial developed leukemia after three years of treatment, the researchers were eager to know the long-term effects of the trial. Sixteen to 18 months after treatment, two puppies maintained the function of the immune system and no side effects occurred.
The results of this study suggest that this in vivo method may not only be a gene therapy for XSCID, but may also be used to treat other hematopoietic and immune diseases, and this method eliminates any possible side effects of the ex vivo manipulation and cultured cell methods. In addition, this approach may also make gene therapy easier and more operable.

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