Gene Therapy: A Revolutionary Technique
Gene therapy is a groundbreaking medical approach that involves altering the genes inside a person’s cells to treat or prevent disease. The idea is to correct, replace, or inactivate defective or missing genes, which are often the root cause of genetic disorders. Essentially, it’s like giving your cells new instructions to make them function correctly.
How Does Gene Therapy Work?
Gene therapy works by:
Replacing a faulty gene with a healthy copy.
Inactivating (or "knocking out") a malfunctioning gene that is causing problems.
Introducing a new gene into the body to help fight disease or repair damage.
The process typically involves using a vector (often a virus) to deliver the new gene into a person’s cells. The virus is modified to carry therapeutic genes but not cause disease.
Types of Gene Therapy
There are several types of gene therapy, but two main approaches based on target cells are:
1. Somatic Gene Therapy
Definition: This targets the non-reproductive cells of the body (somatic cells), like skin cells, muscle cells, liver cells, etc.
Goal: To treat diseases that affect the individual but do not pass the altered genes to future generations.
Example: Treatment for cystic fibrosis or muscular dystrophy. Only the affected tissues or organs are treated, and the gene change won’t be inherited by offspring.
Somatic gene therapy is currently the only type being explored in clinical trials for disorders like:
Cancers
Genetic disorders (e.g., cystic fibrosis, haemophilia)
Blood diseases (e.g., sickle cell anaemia)
2. Germline Gene Therapy
Definition: This involves altering genes in reproductive cells (sperm or eggs) or in the early embryo.
Goal: Changes made in these cells will be passed onto future generations.
Example: If a genetic defect is corrected in a germ cell, the correction will be inherited by offspring.
However, germline gene therapy is controversial due to ethical concerns about permanently altering the human gene pool. Most countries currently ban it in humans because of the risk of unforeseen consequences.
Techniques of Gene Therapy
Gene therapy can also be categorised by how and where the therapeutic genes are delivered:
In Vivo Gene Therapy
Definition: In vivo gene therapy involves directly delivering the therapeutic gene into the patient’s body. The gene is introduced into the target cells inside the body.
How It Works: Viral vectors (e.g., adenoviruses or lentiviruses) are used to deliver the therapeutic gene directly into the bloodstream or affected tissue.
Example: Treatment for muscular dystrophy, where the gene is delivered directly to muscle cells.
Ex Vivo Gene Therapy
Definition: In ex vivo gene therapy, cells are removed from the patient’s body, genetically modified in a lab, and then returned to the patient.
How It Works: Stem cells or other cells are extracted, modified with a therapeutic gene, grown in culture, and then re infused into the patient.
Example: CAR-T cell therapy for cancer, where immune cells are modified to attack cancer cells and reintroduced into the patient.
Delivery Mechanisms: Vector-Mediated and Non-Vector-Mediated Gene Therapy
1. Vector-Mediated Gene Therapy
Definition: This method uses a virus or another vector to deliver the therapeutic gene into cells.
Common Vectors:
Adenoviruses: Effective for short-term expression of the gene.
Retroviruses and Lentiviruses: Integrate the therapeutic gene into the host's genome for long-term expression.
Vectors are modified to carry the therapeutic gene without causing disease.
Example: Adeno-associated viruses (AAV) are used in gene therapy for haemophilia to deliver a functional copy of the clotting factor gene.
2. Non-Vector-Mediated Gene Therapy
Definition: This method does not rely on viruses to deliver the therapeutic gene. Instead, other delivery techniques are used.
Techniques:
Direct DNA injection: DNA is injected directly into the tissue.
Liposomal delivery: Fat-based molecules (liposomes) carry the DNA to the target cells.
Gene editing (CRISPR-Cas9): A cutting-edge technique that directly modifies the target DNA sequence.
Example: CRISPR-Cas9 is used in research to correct mutations responsible for disorders like sickle cell anaemia.
Applications of Gene Therapy
Gene therapy holds promise for treating a wide range of diseases:
Inherited Genetic Disorders: Such as cystic fibrosis, haemophilia, and sickle cell anaemia.
Cancer: By inserting genes that help the immune system recognize and destroy cancer cells.
Cardiovascular Diseases: Introducing genes to promote blood vessel growth in heart disease patients.
Neurological Disorders: Research is ongoing for conditions like Parkinson’s and Huntington’s disease.
Example of Successful Gene Therapy:
One successful example is the treatment for ADA-SCID (also known as “bubble boy” disease). In this rare genetic disorder, children are born without a functioning immune system. Gene therapy has been used to deliver a functional version of the gene responsible for immune function, enabling many children to live normal lives.
Challenges and Ethical Considerations
Safety: Ensuring that the introduced gene integrates correctly and doesn't cause harmful side effects is crucial. Sometimes, the vectors used can trigger immune reactions.
Cost: Gene therapy treatments can be extremely expensive. For example, Zolgensma, a treatment for spinal muscular atrophy, costs millions of dollars.
Ethical Concerns: Particularly with germline gene therapy, there are debates about the ethical implications of altering human genes, especially regarding the potential for "designer babies" – genetically modified to enhance traits like intelligence or physical appearance.
Summary
Gene therapy is a revolutionary approach that seeks to treat genetic diseases at their source by altering faulty genes. It can be delivered through in vivo or ex vivo methods, and via vector-mediated or non-vector-mediated approaches. The two main types are somatic gene therapy (which affects the individual but not their offspring) and germline gene therapy (which could pass changes to future generations). While gene therapy offers immense potential, it also raises significant challenges and ethical considerations.