What's Gene Therapy?
The occurrence of human diseases is mainly caused by the imbalance of metabolism of important substances in the process of life activities or the imbalance of regulation of corresponding signal pathways, among which, part of the diseases are caused by gene expression defects.
Current therapies, whether physical, chemical or biological, aim to restore the body to a state of equilibrium or establish a new equilibrium through the addition of important substances or the control of signaling pathways, with a view to reducing disease symptoms and prolonging the life of patients. The common small molecule chemical drugs and large molecule antibody drugs have achieved great success. But the development of these drugs are also facing many difficulties, such as small molecular medicine with tissue distribution, affinity, and so on. And the targets of antibody drugs are mostly located on the membrane surface, and they are unable to deal with intracellular targets or even nucleic acid targets on chromosomes. Moreover, in order to maintain human homeostasis, therapeutic proteins often need to be imported for a long time, which is a complicated process and difficult to develop. For many patients, lifetime injections are a painful experience.
Therefore, gene therapy has emerged as a therapeutic approach that can achieve the long-term expression of therapeutic proteins and tissue specific expression to achieve the treatment of diseases that cannot be treated with traditional drugs, or significantly improve the way to treat diseases. And because it can target abnormal genes, in some diseases, gene therapy is also thought to cure the disease at its root.
How Gene Therapy Works
In a narrow sense, gene therapy refers to a treatment method that delivers functional genes to patients to correct or replace disease genes. In this treatment method, target genes are introduced into target cells. They either integrate with the host cell chromosome and become part of the host's genetic material, or are located outside the chromosome instead of integrating with the chromosome, but they can be expressed in the cell and play a role in the treatment of disease. In a broad sense, all the methods and principles of molecular biology, carried out at the level of nucleic acid disease treatment can be called gene therapy. So RNA drugs can also be considered gene therapy.
At present, the principle of gene therapy can be divided into the following five:
Gene augmentation: also called genetic supplementation. Introducing exogenous genes into diseased cells or other cells, the expression products of exogenous genes can modify the function of defective cells or enhance some of the original functions, which is one of the most important principles of gene therapy currently on the market and in the experiment. In this treatment, the faulty gene remains in the cell.
Gene replacement/Gene correction: Replace the disease-causing genes in the diseased cells with normal genes in situ, or introduce exogenous normal genes to replace defective genes (point-specific repair), so that the DNA in the cell is completely restored to a normal state. This treatment method is the most ideal in design, but it has not yet broken through in technology, the operation is extremely difficult, and the ethical controversy when used in germ cells is extremely high.
Gene inactivation: Using antisense technology, ribozyme technology or knock-out technology to specifically block gene expression characteristics and inhibit the expression of harmful genes. Drugs such as antisense RNA, ribozymes or RNAi are expected to make breakthroughs in non-transient viral infections and neurological diseases.
Immune adjustment: Introducing genes of antibodies, antigens or cytokines into the patient's body to change the patient's immune status to achieve the purpose of preventing and treating diseases. Drugs can be designed from the two dimensions of humoral immunity and cellular immunity, such as CAR-T.
CAR-T cells are transported to the tumor and proliferate after being transfused into the patient's body
Application of suicide genes: The expression products (enzymes) of certain genes can metabolize non-toxic or low-toxic nucleotide compounds into special intermediate products, and further generate cytotoxic substances to cause cell death. For example, the herpes simplex virus thymidine kinase (HSV-TK) gene is introduced into tumor cells, and then a non-toxic gancidovir (GCV) drug is given to the patient. Because only cells containing the HSV-TK gene can transform GCV into toxic drug, then tumor cells are killed without affecting normal cells.
Application of Gene Therapy
The various principles of gene therapy have been mentioned above. Compared with traditional drugs that directly supplement important substances (proteins, inorganic substances, peptides, etc.) needed by the human body or regulate protein targets in signal pathways, gene therapy has more "upstream" action sites, and treatment is carried out at the nucleic acid level. According to the central principle, diseases caused by protein abnormalities can be treated by the action of nucleic acid in theory. Based on this, the application field of gene therapy is very wide. Some diseases that could not be treated in the past can be cured now, and some diseases with painful and frequent medicine administered have improved solutions. Focus on the following three types of diseases:
1. Genetic diseases: Limited by technology, the main application field of gene therapy is still single-gene genetic diseases, such as SCID, sickle anemia, hemophilia, thalassemia, phenylketonuria, etc. The principle of treatment is genetic modification. Due to the existence of single gene mutations, target cells will produce abnormal proteins or not produce normal proteins. Gene therapy uses viral vectors to introduce exogenous genes into target cells to express normal proteins and achieve therapeutic purposes.
2. Malignant tumors: The treatment principles include gene inactivation, immunomodulation, and suicide genes. The most advanced one is immunomodulation, which includes 3 CAR-T drugs that have been marketed. Gene therapy modifies the recognition proteins on the surface of T cells to activate cellular immunity.
3. Diseases requiring long-term action: Here it refers to diseases that are non-genetic but require long-term action during the treatment process, such as wAMD and dry eye. Using gene transduction to secrete proteins for long time can achieve long-term effectiveness of one-time administration, greatly reduce the pain of administration, and may reduce the total treatment cost.
Gene therapy is a powerful means to treat a variety of diseases. Effective delivery of target genes to the treatment site of the lesion is the key to the success of gene therapy. At present, most commonly used gene carriers are cationic nanoparticles, which can cause cytotoxicity and immune response in the body. The surface of gene carriers usually needs PEG modification to mask part of the positive charge, so as to reduce the non-specific binding of endogenous anionic substances in the blood circulation pathway, prolong the blood circulation time of drug-loaded particles and reduce toxicity.
Gene therapy has brought new treatment opportunities for many diseases that have not been cured so far. It provides unlimited possibilities for the extension of human life span and the improvement of survival rate. As a reliable PEG derivatives supplier, Biochempeg supplies varieties kinds of high purity PEG derivatives to customers worldwide. It is widely used in biological engineering (gene engineering, cell engineering, enzyme engineering, fermentation engineering), biological medicine (recombinant protein drugs, recombinant vaccines, monoclonal antibodies) and other fields.
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