The use of gene therapy to supplement defective genes. Candidates should be able to evaluate the effectiveness of gene therapy.

Gene therapy is when a gene that is missing or not functioning is replaced by one that is.

There are two points at which gene therapy can happen:

• Germ-line: where the genes are changed in a fertilised egg (could be a step towards eugenics)
• Somatic-cell therapy: genes are changed in the affected cells of an adult (pretty ineffective as it must be repeated as cells die, hardly any of the DNA gets expressed and the DNA is not passed on)

There are two ways of changing genes:

• The gene correct gene can be added to cells and a functioning protein will be produced because it is the dominant allele, this is gene supplementation.
• The gene can be replaced altogether (the defective gene removed and the correct one put in).

There are two ways of delivering genes in somatic-cell therapy:

• Using harmless transgenic viruses that inject their recombinant DNA into the affected cells (can create immune response and be rejected)
• Putting the DNA in lipids which can cross the cell surface membrane (liposomes) (can create immune response and be rejected)

Gene therapy can only treat diseases where a single gene is the cause of the problem.

Cystic fibrosis

Cystic fibrosis is a disease where the gene that codes for CFTR has a deletion mutation. CFTR (cystic fibrosis trans-membrane-conductance regulator) is a protein channel that transports chloride ions out of epithelial cells to maintain the water potential and keep membranes moist. Someone with cystic fibrosis who has non-functioning CFTR cannot transport chloride ions out of the cell so does not encourage water to leave the cell resulting in sticky mucus which builds up. Some of the symptoms can be:

• Infertility in males due to blocked sperm ducts
• More frequent infections because pathogens are not removed
• Breathing difficulties
• Cysts made of fibre that is not broken down because pancreatic enzymes can't move down the pancreatic ducts into the duodenum

Viruses used to deliver DNA for cystic fibrosis are adenoviruses because they affect epithelial cells in the lungs, they are introduced to the nose so they are inhaled. The viruses can cause infections. The patient may develop immunity to the virus and so not receive the DNA.

Liposomes are also introduced to the nose, by means of an aerosol. The aerosol may not be fine enough to pass through bronchioles.

SCID

Sufferers of Sever Combined Immunodeficiency cannot coordinate any immune responses because they have a defective gene for ADA (adenosine deaminase) which is meant to kill toxins that kill white blood cells.

It is treated by mixing retroviruses with the DNA for ADA with t-cells from the patient so they inject the DNA and then putting the t-cells back in the patient. Alternatively it is bone marrow cells which are treated which is better because they are stem cells which create t-cells, however it increases the risk of leukaemia.

(When is something a disability? Are disabilities just part of variation?)