'Gene therapy' Near or far?

DSCKII. Bui Van Uy

Recently mentioned " therapeutic genes ". So what is " therapeutic gene " and how will the future help protect health?

The human body has 20,488 genes. Each cell contains all of these genes, but only certain genes work according to certain functions called active genes and functional genes. For example, only mammary cells have an active gene that produces milk. But when under the influence of an element that the gene has abnormal changes, the cell's " life - development - death " process is disrupted, the body becomes ill. " Therapy gene " (using therapeutic gene) means finding ways to control and repair defective and abnormal genes . Many diseases (especially diseases of functional agencies) are ultimately mutated genetic abnormalities, so the " therapeutic gene " is actually an intervention in AND. In theory, epilepsy, Parkinson's, Alzheimer's, schizophrenia, diabetes, blood pressure, cardiovascular disease, and cancer can all use " therapeutic genes ".

Which barriers need to overcome?

Humans have what genes (?) The mechanism of action (?), Which genes are beneficial (active genes, functional genes), which genes are harmful (defective, abnormal genes) ( ?), which effect triggers or restrains genes, transforms genes normally into defective, abnormal genes (?) how to control and repair those genes (?). Decoding the human genome is a huge step forward but only answering the first question, many other questions are still secret. That is the barrier to overcome. Tu Lap Di, genetic researcher, Rector of the University of Hong Kong emphasized: DNA of human cells is extremely complicated. It is true that the cells are damaged and must be repaired. But the repair is very difficult, repairing every cell is even more difficult. Therefore it is far from possible to have " gene therapy ".

What achievement has been achieved?

There are many " therapeutic genes " in animals and humans.

Finding harmful genes or genetic defects that cause disease: Recently found pathogenic genes: such as breast cancer genes (BRCA1, BRCA2, GFR2, TNRC9 MAP3KI, LSPI), genes that cause lung cancer ( TTFI, NKX2-8, PAX9), genes affecting obesity (PTO), Parkinson's disease gene (PINK1). The number of pathogenic genes found is still too small, but it has orientation orientation: if the disease is caused by external agents, it is necessary to take measures to prevent environmental impacts; If the disease is caused by a harmful gene, find a way to act on the gene to control it, destroy it; If the disease is due to a functional gene defect, find ways to activate, or pair the functional gene.

Use functional genes to stimulate organ tissue development. An example: Atherosclerotic coronary artery, which blocks the blood supply, does not provide enough blood for the heart muscle, leading to a heart attack. GS. Jefferey Isner (USA, 1998) injected into the heart muscle of five Vascular Endothelial Growth factor (VEGF) patients. This gene activates, creating new cells that restore sick heart muscle function. Result: heart rate, blood pressure unchanged, no signs of myocardial infarction. After 30 days of injection, all 5 people found that angina was significantly reduced (reducing nitroglycerin vasodilator every day from 7 to 1.5 tablets); after 60 days there is an increase in blood circulation, the appearance of extra capillaries in ischemic areas. Previously, he also succeeded in using VEGF gene to treat a person with leg artery inflammation.

Using genes to stimulate the immune system against harmful cells: Giving the body functional genes that regulate the production of immune-stimulating proteins. Due to the activation of these genes, proteins that stimulate the immune system (such as interferon, interleukin) will be produced in the cancer, capable of producing a remote immune response against cancer. especially metastatic cancer.

Helping the " killer " or angiogenesis gene kill harmful cells: Every normal cell has a pro-caspace-3 that will transform into enzyme caspace-3 that helps cells die (call is an assassin gene or a suicide process. In cancer cells this process does not happen. Illinois researchers (USA) screened from 200 organic compounds that found PAC1 to activate pro-caspace-3, which helps cells commit suicide. In tumors, PCA1 sensitivity increased by 2,000 times compared to other tissue sensitivities, meaning that when using PCA1, the suicide of cancer cells quickly increases.

Cancer cells have genes that regulate neuralgia (new blood vessels born on tumors) from which to take nutrients for cancer cells. Using inhibitors, killing genes that regulate neural arteries, the tumor does not produce neural arteries, the cancer cells do not have new vessels to bring nutrients to feed and die. A generation of drugs that inhibit the growth of bevacizumab, angiostatin, and endostatin, which are formed according to this principle, can prevent the development of cancer metastasis.

Using stem cells instead of diseased cells: Taking stem cells, it is better that cells are differentiated into functional stem cells to inject or graft into the host tissue, they will develop, replacing the host tissue. weakened or ill, restored host tissue function.

The receptor block inhibits growth signaling factor: There is a " gene " in the body that regulates the production of HER2 proteins that act as receptors for growth signaling factors. When for some reason, this " gene " spikes, producing more HER2 proteins, which leads to uncontrolled growth signaling factors, disorganized fast-growing cells that cause cancer. letter. Using herceptin to block HER2 receptors, or using tinib group drugs (eg imatinib, suntinib) inhibits tyrosine kinase (enzymes that play the role of reloading growth signals), inhibiting growth signaling factors , cancer cells do not reproduce (divide), the tumor stops growing, and then is destroyed.

Mercaptopurin is used to treat acute leukemia. In normal people, there is a good gene that produces TPMT enzymes that help break down mercaptopurin. But there are also people who have a bad gene version that does not produce TPMT enzyme, so mercaptopurin does not decompose and accumulates toxic. On the contrary, there are also other bad versions that produce too many enzymes TPMT make mercaptopurin decompose so quickly that it cannot work. The same thing happens with codeine, prozac, statin, warfarin and some other drugs. The scientists placed the patient's DNA (extracted from the blood) and placed the synthetic fiber containing normal AND AND defects on the microchip. Connect the AND. Fluorescence emitted indicates the difference between a patient's gene and a normal gene, thereby making gene use.

Creating genetically modified seedlings that contain drugs and medicine materials: Bringing strange genes into an old seedling, creating genetic mutations, turning into new genetically modified seedlings. This breed contains genes for treating diarrhea, containing anti-diarrhea vaccines, hepatitis vaccines, containing therapeutic substances (selenium, betacarotene) or containing medicinal materials (insulin, a-tryn, epoetin) collectively " agricultural medicine - genetically modified ". An example: Massachusetts-based GTC Biotherapeutiscs uses goats carrying genes that regulate anticoagulant proteins, produce A-tryn, genetic cure without anticoagulants. Prodi Gene produces corn -OMG carrying trypsin gene for insulin production.

Replace the ending

Many scientists in many fields have taken a different approach that does not necessarily sequentially solve each problem in the therapeutic gene. These are unique approaches: genetics, indirect gene understanding; impact on harmful genes, defective genes with drugs; do not repair the gene but insert the stem cell into the host tissue to allow it to develop and replace cells with damaged genes that degrade; Effective evaluation of these practices is not through genes but by clinical judgment.

Gene therapy is a difficult field, as Tu Lap Di said. These new approaches create many paths, many easy-to-do methods, less expensive but effective, most importantly shortening time in applied theory research. So therapeutic genes are not just dreams but have become reality .