Gene therapy

Gene technology and our rapidly increasing knowledge of the positions of particular genes on our chromosomes have given us the opportunity to identify many genes that are responsible for genetic disorders such as sickle cell anaemia and cystic fibrosis.

• the process of inserting 'normal' alleles of genes into cells is known as gene therapy
• it is more difficult than was origianally thought because of the problem  lies in getting normal alleles of the genes into a person's cells and then making them work properly when they get there
• the most common vectors used to carry the normal alleles into host cells are viruses (often retroviruses or lentiviruses) or small spheres of phospholipid called liposomes and occasionally 'naked' DNA is used
• the first successful gene therapy was performed in 1990 on a girl who suffered from the rare genetic disorder known as severe combined immunodeficiency (SCID)
• in this disorder, the immune system is crippled and sufferes die in infancy from common infections
• children showing the condition are often isolated inside plastic 'bubbles' to protect them from infections
• the defect in SCID involves the inability to make an enzyme, adenosine deaminase (ADA) which is vital for the functioning of the immune system
• some of the child's T-lymphocytes were removed and normal alleles of the ADA gene were introduced into them, using a virus as a vector
• the cells were then replaced
• this was not a permanent cure as regular transfusions (every 3 to 5 months) were necessary to keep the immune system from functioning
• 2 years later, gene therapy using stem cells harvested from bone marrow was successful, but in France, in 2000, 4 childdren who had recieved gene therapy for X-linked SCID developed leukaemia as a result of using a retrovirus as vector
• retroviruses insert their genes into the host's genome, but randomly
• meaning they may insert their genes within another gene or, more dangerously, into the regulatory sequence of a gene, which may then activate a nearby gene causing cancer
• since then, researchers used lentiviruses as vectors
• these also insert their genes randomly into the host genome, but they can be modified to inactivate replication
• HIV has been disabled in this way to act as a vector
• the adeno-associated virus (AAV) is also now used as a vector
• this virus does not insert its genes into the host genome and so they are not passed on to daughter cells when a cell divides
• this is a problem when the host cells are short-lived (such as lymphocytes), but the virus has been used successfullly with long-lived cells such as liver cells and neurones

This work on vectors has led to increasingly successful gene therapies in the last few years, including the following:

• The eyesight of young men with a form of hereditary blindness, Leber congeital amaurosis, in which retinal cells die off gradually from an early age, has been improved
• The normal allele of the B-globin gene has been successfully inserted into blood stem cells to correct the disorder, B-thalassaemia
• Six people with…