Treatment of a genetic disorder by altering a patient's genotype. This treatment is done by inserting normal genes into the patient's cells using a vector.
A vector in this context is like an agent who carries the normal genes into human body cells.
- Examples of vectors : Modified and weakened viruses (it is often a retroviruses or lentiviruses which causes AIDS ) or small spheres of phospholipid called Liposomes
Occasionally , a 'naked' DNA is used for vectors to carry them into the body cells.
Naked plasmid DNA is an attractive non-viral gene vector because of its inherent simplicity and because it is easily produced in bacteria and manipulated using standard recombinant DNA techniques.
Genetic Diseases cured by Gene Therapy
1. Short Term Memory Loss (Etc : Alzheimer's disease in mice)
Researchers have prevented the development of Alzheimer's disease in mice by using a virus to deliver a specific gene into the brain. (For more Info)
2. SCID (Severe Combined Immunodeficiency)
- This disorder causes one's immune system to cripple and eventually death in infancy from common infections.
- Children showing the condition are often isolated inside 'plastic bubbles' to shield them from infections.
What causes the defect in a SCID patient?
The inablility of patient's cells to make an enzyme adenosine deaminase (ADA) which is vital for the functioning of the immune system.
How did gene therapy solved the inability?
Back in 1990 was the first successful gene therapy on a four year old girl from Cleveland, Ohio. This therapy was performed by removing some of the child's white blood cells (T-Lymphocytes) and normal alleles of the ADA gene were introduced into them(the white blood cells) using a virus as a vector. The cells were then replaced.
This was not a permanent cure because white blood cells have a short lifespan ranging form a week to a few months. Therefore, regular transfusions(every 3 to 5 months) were necessary to keep the immune system functioning.
Two years later, gene therapy using stem cells harvested from bone marrow was a success.
But.......... there are two sides to every coin,
Four children who had received gene therapy for X-linked SCID developed leukaemia as a result of using retrovirus as the vector for this treatment.
- Retroviruses insert their genes into the host's genome (randomly).
- This means that they may insert their genes into the regulatory sequence of a gene, which may then activate a nearby gene causing cancer (Uncontrolled cell division)
Since then, researchers have used lentiviruses as vectors which acts similarly to Retroviruses, but they can be modified to inactivate replication [Replication of viruses= Making new copies of viruses like a photocopier machine]
- HIV (Human immunodeficiency Virus) has been disabled in this way so that they can act as a vector.
- The adeno-associated virus (AAV) is also now used as a vector.
- This virus does not insert its genes (normal genes) into the complete set of genetic material present in the patient and so they are not passed on to newly formed cells when the cell divides.
- This is the main problem when the host cells are short lived (Such as lymphocytes stated above), But the virus has been used successfully with long-lived cells such as liver cells and nerve cells.