Abi Starr
16.5 Gene Therapy
Around 2% of the human population are affected by one of 4000 diseases caused by a missing gene
or a gene that is not expressed properly. An example of this is cystic fibrosis. A potential cure is to
replace faulty genes with those cloned from healthy individuals in a technique called gene therapy.
Gene therapy has lots of potential uses, including the treatment of cancer. In 2008, a young man
with a type of genetic blindness had his sight partially restored using gene therapy.
Cystic fibrosis
CF is the most common genetic disorder among the white population of Europe and North America,
around one in 20,000 people have it. It is caused by a mutant recessive allele in which 3 DNA bases
(A, A, A) are missing. Because of this, it is an example of a deletion mutation. The normal gene,
called the Cystic fibrosis trans-membrane-conductance regulator (CFTR) gene, normally produces a
protein formed of 1,480 amino acids. The deletion results in one amino acid being left out of the
protein. This is enough to make the protein unable to perform its role of transporting chloride ions
across epithelial membranes. CFTR is a chloride-ion channel protein that transports chloride ions out
of epithelial cells, and water naturally follows by osmosis. In this way, epithelial membranes are kept
moist.
In a CF patient, the defective gene means that the protein is either not made at all or does not
function properly. The epithelial membranes are therefore dry and the mucus they produce remains
viscous and sticky. The symptoms this causes include:
Mucus congestion in the lungs – this leads to a much higher risk of infection because the
mucus (that traps disease causing microorganisms) cannot be removed
Breathing difficulties and less efficient gaseous exchange
Accumulation of thick mucus in the pancreatic ducts- this prevents pancreatic enzymes from
reaching the duodenum and leading to the formation of fibrous cysts
Accumulation of thick mucus in the sperm ducts in males – this could cause infertility
As CF is caused by a recessive allele, it is possibly that two seemingly normal parents could have a
child that suffers from the disease. Where there is a history of the disease in both families, the
parents may choose to be genetically screened to see if they carry the allele or not.
Treatment of CF using gene therapy
There are two ways in which gene therapy can be used to treat CF:
Gene replacement – In which the defective gene is replaced with a healthy one
Gene supplementation – In which one or more copies of the healthy gene are added
alongside the defective gene. As the added genes have dominant alleles, the effects of the
recessive alleles of the defective gene are masked.
In addition, there are two different techniques of gene therapy that could be used, according to
which type of cell is being treated:
Germ line gene therapy – This involves replacing or supplementing the defective gene in the
fertilised egg. This ensures all cells of the organism will develop normally, as will all the cells
of their offspring. Therefore, this is a much more permanent solution, affecting future
generations as well as the initial patient. However, the moral and ethical issues of
manipulating such a long term genetic change mean that the process is currently prohibited.
Page 1 of 4
16.5 Gene Therapy
Around 2% of the human population are affected by one of 4000 diseases caused by a missing gene
or a gene that is not expressed properly. An example of this is cystic fibrosis. A potential cure is to
replace faulty genes with those cloned from healthy individuals in a technique called gene therapy.
Gene therapy has lots of potential uses, including the treatment of cancer. In 2008, a young man
with a type of genetic blindness had his sight partially restored using gene therapy.
Cystic fibrosis
CF is the most common genetic disorder among the white population of Europe and North America,
around one in 20,000 people have it. It is caused by a mutant recessive allele in which 3 DNA bases
(A, A, A) are missing. Because of this, it is an example of a deletion mutation. The normal gene,
called the Cystic fibrosis trans-membrane-conductance regulator (CFTR) gene, normally produces a
protein formed of 1,480 amino acids. The deletion results in one amino acid being left out of the
protein. This is enough to make the protein unable to perform its role of transporting chloride ions
across epithelial membranes. CFTR is a chloride-ion channel protein that transports chloride ions out
of epithelial cells, and water naturally follows by osmosis. In this way, epithelial membranes are kept
moist.
In a CF patient, the defective gene means that the protein is either not made at all or does not
function properly. The epithelial membranes are therefore dry and the mucus they produce remains
viscous and sticky. The symptoms this causes include:
Mucus congestion in the lungs – this leads to a much higher risk of infection because the
mucus (that traps disease causing microorganisms) cannot be removed
Breathing difficulties and less efficient gaseous exchange
Accumulation of thick mucus in the pancreatic ducts- this prevents pancreatic enzymes from
reaching the duodenum and leading to the formation of fibrous cysts
Accumulation of thick mucus in the sperm ducts in males – this could cause infertility
As CF is caused by a recessive allele, it is possibly that two seemingly normal parents could have a
child that suffers from the disease. Where there is a history of the disease in both families, the
parents may choose to be genetically screened to see if they carry the allele or not.
Treatment of CF using gene therapy
There are two ways in which gene therapy can be used to treat CF:
Gene replacement – In which the defective gene is replaced with a healthy one
Gene supplementation – In which one or more copies of the healthy gene are added
alongside the defective gene. As the added genes have dominant alleles, the effects of the
recessive alleles of the defective gene are masked.
In addition, there are two different techniques of gene therapy that could be used, according to
which type of cell is being treated:
Germ line gene therapy – This involves replacing or supplementing the defective gene in the
fertilised egg. This ensures all cells of the organism will develop normally, as will all the cells
of their offspring. Therefore, this is a much more permanent solution, affecting future
generations as well as the initial patient. However, the moral and ethical issues of
manipulating such a long term genetic change mean that the process is currently prohibited.
Page 1 of 4
