The Current Status and Prospects of Gene Therapy-Gene Therapy
The clinical trials of human cell gene therapy have begun. The following conditions must be met for gene therapy:
① Select appropriate diseases and have a clear understanding of their pathogenesis and the structure and function of corresponding genes;
② The gene for correcting the disease has been cloned, and the mechanism and conditions of gene expression and regulation are understood;
③ This gene has suitable receptor cells and can be effectively expressed in vitro;
④ Having safe and effective transfer carriers and methods, as well as available animal models.
In the past three years, clinical gene therapy has been carried out for several human monogenic genetic diseases and tumors.
1.Gene therapy for complex immunodeficiency syndrome
In 1991, the United States approved the first program of somatic gene therapy for genetic diseases, which involved introducing adenosine deaminase (ADA) into a 4-year-old girl with severe composite immunodeficiency syndrome (SCID). The indirect method used is reverse transcription virus mediated, which involves culturing white blood cells from pediatric patients using a reverse transcription virus vector containing the normal human adenosine deaminase gene, and stimulating their proliferation with interleukin-2 (IL-2). After about 10 days, the cells are then intravenously infused into the pediatric patients. Approximately once every 1-2 months of treatment, after 8 months, the ADA level in the child's body reached 25% of the normal value, and no significant side effects were observed. Afterwards, a second treatment was performed to achieve similar results.
2.Gene therapy for melanoma
Gene therapy for tumors has long been expected by people. Based on various explorations, the role of tumor infiltrating lymphocytes (TILs), which can persist in the tumor site without side effects, has been discovered in tumor treatment. In 1992, the TNF/tumor cell and IL-2/tumor cell protocols were implemented, which involved introducing the IL-2 gene tumor necrosis factor (TNF) gene into tumor cells cultured from the patient's own body. These cultured tumor cells were then injected into the patient's buttocks. Three weeks later, the injection site and its draining lymph nodes were excised, and T cells were cultured under suitable conditions. The amplified T cells were combined with IL-2 and used in the patient. As a result, one out of five melanoma patients had complete tumor regression, two had 90% tumor regression, and the other two died nine months after treatment. Due to the accumulation of TNF carrying TIL at the tumor site, the application of TIL enhances its killing effect on tumors.
3.Gene therapy for other genetic diseases
Other genetic diseases such as cystic fibrosis, which is common in Caucasians, progress rapidly. For gene therapy of DMD, some progress has also been made due to the existence of mouse animal models. For example, in 1993, France successfully injected Ad RSVmDys (adenovirus Ross virus small muscle malnutrition protein gene recombinant) into mouse muscles. Even using adenovirus as a vector, the cDNA of the minidystrophin gene was recombined and injected into the muscle of mdy mice under the RSV promoter. It has been proven that it can be expressed in the muscle of mdy mice. In addition, exploration is underway for some genetic diseases such as hemophilia, thalassemia, and Gaucher's disease.
Fudan University and other institutions in China have also made meaningful explorations in gene therapy for hemophilia B. Based on a rabbit model, they introduced the human factor IX gene into autologous skin fibroblasts through recombinant plasmids (pcmvix) or recombinant retroviruses (N2CMVIX), achieving promising results. It is believed that gene therapy will be successful in China in the near future.
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