GENE THERAPY

Genes are segments in the DNA that supply the body with instructions, directing the cell to produce
proteins that perform a vast array of functions in the body. A defective gene may result to (a) the
failure of protein production, (b) the production of a non-functional protein, or (c) the over production of
a protein, all of which lead to some sort of a disease or disorder.

Gene therapy is an experimental treatment that involves the insertion of a gene to correct the
effects of a defective gene. Recently, gene therapy has also been used to treat an illness caused in
some other way.

1. Types of Gene Therapy

a. Somatic gene therapy
- transfer of a gene to any cell of the body that does not produce sperms or eggs
- the effects of gene therapy will not be passed onto the patient’s children
b. Germline gene therapy
- transfer of a gene to cells that produce eggs or sperm
- the effects of gene therapy will be passed onto the patient’s children

2. Gene Therapy Techniques

a. Gene augmentation therapy
- if a required protein is absent or non-functional due to a defective gene, a functional gene is
inserted to produce that required protein
* example: Cystic fibrosis
- a fatal disease due to a defective gene that produces a non-functioning plasma
membrane protein
- results to over production of mucus that blocks the bronchi, pancreatic ducts, or
intestines
- insertion of a functional gene can produce the required normal plasma proteins

b. Gene inhibition therapy

- if protein products of a defective gene encourages the proliferation of disease-related cells,
a new gene is inserted to either block the defective gene or the activity of the protein product
* example: Cancer
- a mutation of the oncogene (gene that stimulates cell growth) leads to over-activation
- results to the production hyperactive proteins that allow cells to undergo unregulated
growth and proliferation
- insertion of a new gene can block the oncogene to prevent further cell growth and
stop the cancer in its tracks
c. Killing of specific cells
- targets diseased cells for death in one of two ways:
c.1 Insertion of a “suicide” gene that produces a toxic protein product killing the diseased cell
c.2 insertion of a gene that produces a protein which marks the diseased cell for attack by the
body’s immune system cells
* example: Cancer cells
3. Overview of the Steps in Gene Therapy
a. identification of affected gene
b. cloning the required gene
c. loading the vector with the required gene
- the more promising system of gene delivery at the moment is the use of viral vectors
- they are genetically engineered to remove their viral genes (rendering them harmless) and
replaced with the required gene for delivery
d. vector injected into the target cell
e. vector delivers the gene into the nucleus of the target cell
- gene may or may not be incorporated into the DNA of the cell
f. delivered gene performs its function
- gene is expressed by the cell’s normal machinery leading to production of the required
protein and the eventual treatment of the patient’s disease

4. Challenges of gene therapy

a. Targeting the right cells
- it is crucial that the delivered gene reaches the right cell
- delivering into the wrong cell could cause more health problems
b. avoiding the immune response
- a new gene is considered an intruder that could spark an immune response
c. making sure the delivered gene does not disrupt the other genes
- the delivered gene may insert itself in the path of another gene, disrupting its activity
d. high cost of gene therapy
- an individual case-by-case approach may be very expensive
- only the wealthy can afford the therapy
e. moral and ethical issues
- are we playing God?
- what is a human being?
- germline gene therapy: the unborn cannot decide for itself