Key Challenges and Advances in Modern Gene Therapy
With the advancement of medical science, several treatments have been discovered to treat deadly diseases. However, there are a few diseases that are genetic and as a result, are not easily curable. In a few such cases, the application of gene therapy has been found to be useful.
It is an experimental technique through which healthy genes are inserted into an individual or embryo to treat disease. Gene therapy paves ways to replace faulty or mutated genes with new ones.
To know how to define gene therapy, continue reading this article.
How does Gene Therapy Works?
There are several ways through which gene therapy works.
Replace a mutated gene with a healthy version of that gene.
Introduce a new functioning gene to fight disease.
Inactivate a faulty gene that is causing disease.
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This gene therapy diagram shows that first, the defective genes are spotted. Then, medical experts use healthy genes to replace faulty ones. Finally, the new gene restores the functionality of the existing cells. Some portions of DNA containing useful proteins enter the cells through the vectors. Inside the cell, DNA/genes start making useful proteins. After some time, the damaged cells heal and remove the source of the disease.
The next segment focuses on the varied application of gene therapy.
Different Kinds of Gene Therapy
Primarily, there are two types of gene therapy.
Somatic Gene Therapy
The human body mainly consists of somatic or stem cells. This process uses healthy genes to replace damaged ones. The therapy targets the defective cells of an individual who is suffering from a disease. Somatic cells are mainly non-reproductive. That means the effects of this therapy will not transfer to the future generation. Hence, it is considered to be one of the safest applications of gene therapy.
Germline Gene Therapy
This therapy targets the germ cells of the body that produce eggs or sperms. Germline gene therapy process includes the infusion of functional DNA into cells. However, the effect of this therapy can affect future generations. Therefore, the usage of this therapy is restricted in many places. For example, the European Union does not allow this process.
Gene Therapy Application
With time, the popularity of this therapy is increasing. The application of gene therapy includes the following:
Effectively cures several genetic disorders.
Treats diseases like brain tumours, Alzheimer’s, Parkinson’s, Haemophilia, and several others.
Useful for the diseases that traditional medicine cannot cure.
Solely destroys disease-causing cells without affecting other cells.
Can be used on individuals, as well as embryos.
However, this treatment has some temporal or permanent side effects too.
Do it yourself: Make a detailed note on the harmful effects of gene therapy.
Challenges of Gene Therapy
The new genes have to reach the right place.
On reaching the exact location, this gene has to start becoming functional.
The genes can cause harm if they reach the wrong cells.
Sometimes targeted cells stop the new genes from entering. The immune system of a body often also tries to kill the inserted gene.
It has to make sure that the new cells are affecting the functions of other cells.
In short, gene therapy can be an excellent treatment option if used properly.
Multiple Choice Questions
1. Somatic cell therapy involves…
Ex vivo
In vivo
Antisense
All of these
2. Which one of these causes a mutation in a single gene?
HIV
Colon cancer
Cystic Fibrosis
Diabetes
3. Which one helps in treating cancer?
In vivo
Ex vivo
Antisense
All of the above
4. ADA deficiency in children can be treated by?
Bone marrow transplantation
Gene therapy
Chemotherapy
Antisense therapy
Answers: 1-D), 2-C), 3-C), 4-A)
Gene Therapy Products
Plasmid DNA - Therapeutic genes may be genetically built into circular DNA molecules and delivered to human cells.
Viral Vectors - Several gene therapy products are generated from viruses because viruses have the inherent capacity to transport genetic material into cells. Once viruses have been engineered to lose their potential to cause infectious illness, they can be employed as vectors (vehicles) to deliver therapeutic genes into human cells.
Bacterial Vectors - Bacteria can be altered to avoid producing infectious illness and then utilised as vectors (vehicles) to deliver therapeutic genes into human cells.
Human gene Editing Technology - Gene editing aims to either disrupt dangerous genes or fix mutated genes.
Patient-derived Cellular Gene Therapy Products - Cells are extracted from the patient, genetically changed (typically with the use of a viral vector), and then returned to the patient.
Disadvantages of Gene Therapy
DNA Mutations - The new gene might be placed in the incorrect place in the DNA, resulting in dangerous DNA alterations or even cancer.
Immune Response - The body's immune system may recognize the newly added viruses as invaders and attack them, resulting in inflammation, toxicity, and, in severe cases, organ failure.
Viral Spread - Because viruses may impact several types of cells, it is likely that the viral vectors will infect cells other than those with altered or absent genes. If this occurs, healthy cells may be destroyed, resulting in sickness or disease, including cancer.
Risk to Offspring - The altered DNA might have an impact on reproductive cells, such as egg cells in women and sperm cells in men. This might lead to genetic alterations in children born after the therapy.
Reversion of the virus to its Original Form - When viruses are introduced into the body, they may regain their potential to cause disease.
High cost
Potential for short-term efficacy
Which Diseases does Gene Therapy Treat?
Several gene therapies have been authorised by the FDA. CAR T-cell therapy is one of the first, and it's exclusively for children and young people with B-cell acute lymphoblastic leukaemia, who have failed to respond to prior therapies. In Europe, a treatment for lipoprotein lipase deficiency, a condition in which a person is unable to break down fat molecules, was authorised as the first gene therapy in 2012.
Another treatment for severe combined immune deficiency (also known as "bubble boy" syndrome) might be available in Europe very soon. Experiments have shown promising outcomes for a variety of additional ailments, that includes – Haemophilia. Some cause blindness, immune deficiencies, muscular dystrophy. Many more clinical studies are now underway, many of which are for uncommon diseases.
FAQs on Gene Therapy Explained: Mechanisms, Types & Applications
1. What is gene therapy and what is its primary purpose?
Gene therapy is a medical technique that aims to treat or cure diseases by correcting or replacing a person's defective or malfunctioning genes. Its primary purpose is to introduce a normal, functional gene into an individual's cells to compensate for an abnormal one, thereby restoring the normal function of a protein and alleviating the symptoms of a genetic disorder.
2. What are the two main types of gene therapy?
The two principal types of gene therapy are distinguished by the type of cells they target:
Somatic Gene Therapy: This involves introducing a therapeutic gene into the somatic (body) cells of an individual, such as bone marrow or liver cells. Any genetic changes are confined to the individual patient and are not passed on to their children.
Germline Gene Therapy: This involves modifying the genes in reproductive cells (sperm or eggs) or in an early embryo. These changes would be heritable and passed on to subsequent generations. Due to major ethical concerns, germline therapy is not performed on humans.
3. What is the general process involved in gene therapy?
The general process of gene therapy typically involves several key steps:
Diagnosis: A doctor identifies a disease caused by a specific faulty gene.
Gene Isolation: A normal, functional version of the faulty gene is isolated and cloned to produce many copies.
Vector Packaging: The functional gene is inserted into a delivery vehicle, called a vector, which is often a modified, harmless virus.
Delivery: The vector carrying the gene is introduced to the patient's target cells, either directly into the body (in vivo) or by treating cells in a lab and returning them to the patient (ex vivo).
Expression: The new gene integrates into the cells' DNA and begins to produce the correct, functional protein, treating the disease.
4. What are some important examples of diseases that can be treated with gene therapy?
Gene therapy has shown promise for a range of genetic disorders and other diseases. A classic example from the NCERT syllabus is the treatment of Adenosine Deaminase (ADA) Deficiency, a form of Severe Combined Immunodeficiency (SCID). Other examples include:
Haemophilia
Cystic Fibrosis
Sickle Cell Anemia
Certain types of cancer (e.g., CAR-T cell therapy)
5. Why are viruses commonly used as vectors in gene therapy?
Viruses are commonly used as vectors because they have a natural ability to enter host cells and insert their own genetic material into the host's genome. Scientists exploit this mechanism for gene therapy by modifying the virus to be safe. They remove the virus's own disease-causing genes and replace them with the therapeutic human gene. This 'disarmed' virus then acts as a highly efficient delivery vehicle to transport the correct gene into the patient's cells. Common viral vectors include retroviruses and adenoviruses.
6. What is the difference between in vivo and ex vivo gene therapy mechanisms?
The key difference lies in where the genetic modification of cells occurs:
Ex vivo (outside the body): In this method, a patient's cells (e.g., bone marrow stem cells) are removed from their body. These cells are then genetically modified in a laboratory by introducing the therapeutic gene. After successful modification, the corrected cells are cultured and infused back into the patient.
In vivo (inside the body): In this method, the vector carrying the therapeutic gene is injected or delivered directly into the patient's body, where it travels to the target cells and delivers the gene within the natural environment of the body.
7. What are the major risks and ethical concerns associated with gene therapy?
While promising, gene therapy has significant challenges. Risks include unwanted immune responses to the vector, the gene being delivered to the wrong cells, and the risk of the new gene inserting into the wrong location in the DNA, potentially causing cancer (insertional mutagenesis). Ethical concerns primarily revolve around germline therapy and its potential to alter the human gene pool permanently. There are also debates about its high cost, accessibility, and the potential for it to be used for non-therapeutic genetic enhancement rather than treating diseases.
8. Once a therapeutic gene is delivered to a cell, how does the cell actually use it to correct a defect?
Once the therapeutic gene is successfully delivered into a target cell's nucleus, it functions by using the cell's own natural machinery. The cell's enzymes read the DNA sequence of the new gene through a process called transcription to create a messenger RNA (mRNA) molecule. This mRNA then travels out of the nucleus to the ribosomes, where it is used as a template in a process called translation to build the correct, functional protein. This newly produced protein then performs its intended function, compensating for the faulty protein and correcting the cellular defect.
