Revolution in genetic therapy: a new era in the treatment of diseases
Section 1: Fundamentals of genetic therapy: Co -rewriting the code of life
Genetic therapy, in fact, is a change in the genetic material of the patient’s cells for the treatment or prevention of diseases. This advanced approach promises to revolutionize medicine, opening doors for the treatment of diseases that were previously considered incurable. Instead of simply treating symptoms, genetic therapy is aimed at eliminating the cause of the disease at the genetic level.
1.1 Central dogma of molecular biology and its connection with genetic therapy:
The central dogma of molecular biology describes the flow of genetic information in a living cell: DNA → RNA → protein. DNA contains a genetic code that is transcribed in RNA, and RNA is then broadcast into proteins. Proteins, in turn, perform most cellular functions. Many diseases occur due to defects in DNA, which lead to the production of non-functional or missing proteins. Genetic therapy uses this flow of information to correct genetic defects and restore the normal function of cells.
1.2 Types of genetic therapy:
There are two main types of genetic therapy:
- Somatic genetic therapy: In this type of therapy, genetic changes are introduced into somatic cells (any body cells, except for the germ cells). Changes made to somatic cells are not transmitted to the next generation. Этот тип терапии наиболее распространен и используется для лечения широкого спектра заболеваний.
- Generate genetic therapy: In this type of therapy, genetic changes are introduced into the germ cells (spermatozoa or eggs) or to early embryos. Changes made to the genital cells will be transmitted to the following generations. Зародышевая генная терапия вызывает серьезные этические споры и в настоящее время не используется в клинической практике из-за потенциальных рисков и неопределенностей.
1.3 approaches to genetic therapy:
In the framework of somatic genetic therapy, there are various approaches that are used to deliver genetic material to patient cells:
- General additive: This approach includes the introduction of a functional copy of the gene into the patient’s cells in order to compensate for a defective or absent gene. This is the most common approach to genetic therapy.
- Gennous jamming: This approach includes the introduction of a molecule that blocks the expression of a defective gene. This approach is used to treat diseases caused by excessive gene expression or toxic protein expression.
- Gene editing: This approach includes the use of tools such as CRISPR-CAS9 for accurate editing DNA in patient cells. This approach allows you to correct defective genes or insert new genes into certain places in the genome.
- Genes carriers: This approach includes modifying the patient’s cells outside the body (ex vivo), and then the introduction of these modified cells back into the body. This approach is often used to treat cancer, where the cells of the immune system are modified for a more effective attack on cancer cells.
Section 2: Vectors: Vehicles for Genes delivery
Vectors play a decisive role in genetic therapy, acting as vehicles for the delivery of genetic material to the patient’s cells. The choice of a suitable vector is important for ensuring the effectiveness and safety of genetic therapy.
2.1 Vector types:
There are two main types of vectors used in genetic therapy:
- Viral vectors: Viruses are natural carriers of genetic material, and they were modified for use as gene therapy vectors. Viral vectors have a high efficiency of cell infection, but they can also cause immune reactions and other side effects. The most common types of viral vectors include:
- Adenoassed viruses (AAV): AAV are safe and effective vectors that can infect a wide range of cells. They are widely used in genetic therapy.
- Adenoviruses: Adenoviruses are less safe than AAV, but they are able to infect a wider spectrum of cells. They are often used to treat cancer.
- Retrovirus: Retroviruses are able to integrate their genetic material in the genome of the host cell, which ensures prolonged expression of the gene. However, they can also cause mutations and cancer.
- Lentviruses: Lentviruses are a subtype of retroviruses that are able to infect both dividing and weekly cells. Они широко используются в генетической терапии.
- Herpes simplex virus (HSV): HSV is a virus that infects nerve cells. It is often used to treat diseases of the nervous system.
- Nevirus vectors: Nevirus vectors do not use viruses to deliver genetic material. They, as a rule, are less effective than viral vectors, but they are also less likely to cause immune reactions. The most common types of non -viral vectors include:
- Plasmids: Plasmids are DNA ring molecules that can be introduced into cells using electrophy or other methods.
- Liposomes: Liposomes are small spherical vesicles consisting of lipid membranes. They can be used to encapsulate genetic material and delivery to cells.
- Nanoparticles: Nanoparticles are small particles that can be used to deliver genetic material to cells. They can be made of various materials such as lipids, polymers or inorganic materials.
2.2 The choice of vector:
The choice of a suitable vector for genetic therapy depends on several factors, including:
- Type of disease: Some vectors are more effective for treating certain diseases than others.
- Type of target cells: Some vectors are able to infect only certain types of cells.
- Immune answer: Some vectors are more likely to cause an immune response than others.
- Safety: The security of the vector is the most important factor when choosing a vector for genetic therapy.
2.3 Engineering solutions to improve vectors:
New strategies are constantly being developed to improve the efficiency and safety of gene therapy vectors. These strategies include:
- The orientation of the vector:
- Reducing immunogenicity: Modification of the vector to reduce the likelihood of causing an immune response.
- Increase in genes expression: Modification of the vector to increase the amount of protein produced by the genome that it carries.
Section 3: Gene editing: accurate surgery at the DNA level
Gene editing is a revolutionary technology that allows scientists to accurately edit DNA in cells. This powerful tool opens up new opportunities for the treatment of genetic diseases, as well as for the development of new methods of diagnosis and prevention of diseases.
3.1 CRISPR-CAS9: New generation genome editor:
CRISPR-CAS9 (Clustered Regularly Interspaced Short Palindromic Repeats and CrisSoSociated Protein 9) is the most widely used gene editing system. It consists of two components:
- Red9: CAS9 is an enzyme that acts as molecular scissors, cutting DNA in a certain place.
- RNA guide (GRNA): GRNA is a short RNA molecule that directs CAS9 to a certain place in the genome. GRNA is complemented by the DNA sequence, which must be edited.
When the GRNA associates with a complementary DNA sequence, CAS9 cuts DNA in this place. Then the cell activates its own DNA reparation mechanisms to restore the gap. In the process of DNA reparation, changes can be made, such as insert or removal of nucleotides. This allows scientists to correct defective genes, insert new genes or turn off certain genes.
3.2 other genetic editing tools:
In addition to CRISPR-CAS9, there are several other gene editing tools that are also used in scientific research and clinical trials, including:
- ZFN (Zinc Finger Nucleases): ZFN are artificial enzymes of restrictions that can cut DNA in certain places.
- TALEN (Transcription Activator-Like Effector Nucleases): Talen also represent artificial enzymes of restrictions that can cut DNA in certain places.
3.3 Application of genetic editing:
Gene editing has a wide range of applications in medicine, agriculture and biotechnology.
- Treatment of genetic diseases: Gene editing can be used to correct defective genes that cause genetic diseases, such as cystic fibrosis, sickle cell anemia and Huntington disease.
- Development of new drugs: Gene editing can be used to create cellular models of diseases that can be used to test new drugs.
- Creation of agricultural crops resistant to diseases: Gene editing can be used to create agricultural crops resistant to diseases and pests.
- Production Bio -Topliva: Gene editing can be used to improve biofuel production.
3.4 Ethical considerations:
Gene editing causes serious ethical considerations, especially with regard to editing the embryo line. Editing the embryo line will lead to changes in DNA, which will be transmitted to the next generation. This causes concerns about the unforeseen consequences and potential abuse of technology. There is also a fear that genetic editing can be used to improve people, and not only for the treatment of diseases.
Section 4: Application of genetic therapy: from laboratory table to clinical practice
Genetic therapy has come a long way from the laboratory table to clinical practice. Currently, there are several genetic therapies approved for the treatment of various diseases, and many others are at the development stage.
4.1 approved genetic therapy:
- Luxury: Luxturna is a genetic therapy for the treatment of hereditary retinal dystrophy caused by mutations in the RPE65 gene.
- Zlensma: Zolgensma is a genetic therapy for the treatment of spinal muscle atrophy (SMA), a rare genetic disease that causes weakness and muscle atrophy.
- Onasemnogenic Abparvovec: OnaseMnogene ABEPARVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVOVAM is a genetic therapy used to treat spinal muscle atrophy (SMA) in children under two years of age. Therapy includes the introduction of a functional copy of the SMN1 gene, which is absent or defective in patients with SM.
4.2 Genetic therapy in clinical trials:
Many genetic therapy are currently in clinical trials for the treatment of a wide range of diseases, including:
- Cancer: Genetic therapy is used to treat various types of cancer, including leukemia, lymphoma and melanoma.
- Hemophilia: Genetic therapy is used to treat hemophilia A and hemophilia B, hereditary blood coagulation disorders.
- MukoviScidoz: Genetic therapy is used to treat cystic fibrosis, a genetic disease that affects the lungs and other organs.
- Parkinson’s disease: Genetic therapy is used to treat Parkinson’s disease, a neurodegenerative disease that affects motor skills.
- Alzheimer’s disease: Genetic therapy is used to treat Alzheimer’s disease, a neurodegenerative disease that affects memory and cognitive functions.
4.3 Advantages of genetic therapy:
Genetic therapy has several advantages compared to traditional treatment methods, including:
- Potential for curing diseases: Genetic therapy can provide a cure for diseases that were previously considered incurable.
- A longer effect: Genetic therapy can provide a longer effect than traditional treatment methods.
- Less side effects: Genetic therapy can have less side effects than traditional methods of treatment.
4.4 Problems of genetic therapy:
Genetic therapy is also associated with a number of problems, including:
- High cost: Genetic therapy can be very expensive, which makes it inaccessible to many patients.
- Safety problems: Genetic therapy can have side effects, such as the immune response and the development of cancer.
- Delivery problems: Delivery of genetic material to target cells can be a difficult task.
- Ethical considerations: Gene therapy causes serious ethical considerations, especially with regard to editing the embryo line.
Section 5: The future of genetic therapy: new horizons and prospects
Genetic therapy is a rapidly developing area, and further breakthroughs should be expected in the future. New technologies and approaches will expand the range of diseases that can be treated with genetic therapy, as well as increase the efficiency and safety of this therapy.
5.1 New technologies:
- Improved vectors: New vectors are developed that are more effective and safe than existing vectors.
- More accurate gene editing tools: More accurate gene editing tools are developed, which allow you to edit DNA with greater accuracy and fewer side effects.
- New delivery methods: New methods of delivery of genetic material to target cells, such as nanoparticles and exosomas, are developed.
5.2 Prospects:
- Personalized medicine: Genetic therapy can be used to develop personalized treatment methods that are adapted to the individual genetic characteristics of each patient.
- Preventive medicine: Genetic therapy can be used to prevent diseases by correcting genetic defects before they cause the disease.
- Increase in life expectancy: Genetic therapy can be used to increase life expectancy by slowing down the aging process.
5.3 Regulation and ethics:
The regulation and ethics of genetic therapy play an important role in ensuring the safety and effectiveness of this therapy. Необходимо разработать строгие правила, чтобы предотвратить злоупотребление этой технологией и защитить права пациентов. It is also necessary to conduct wide public discussions of ethical issues related to genetic therapy in order to ensure its responsible use.
5.4 Conclusion:
Genetic therapy is a revolutionary technology that promises to change medicine. It opens up new opportunities for the treatment and prevention of diseases, as well as for improving the health and life expectancy of people. Despite the existing problems, genetic therapy has great potential to improve the quality of life of people around the world. The development of new technologies, strict rules and a wide public discussion of ethical issues will contribute to the safe and effective use of genetic therapy in the future.