Download Gene Therapy - Farmasi Unand

Kuliah I
14 Maret 2011
Gene Therapy
Prof. Dr. Marlina, MS, Apt
Mata Kuliah: Bioteknologi Farmasi
What is a gene?
A gene is a discrete sequence of DNA that contains
information to make a protein.
Sometimes a gene can be defective or missing.
A defective gene may cause a protein that doesn’t
work correctly to be made.
A missing gene may mean essential proteins aren’t
made.
What is gene therapy?
Gene therapy is correcting functional gene loss by
delivering genes to human tissues or simply
expression of a "therapeutic gene" in a target tissue
to achieve benefit.
Often DNA viruses engineered to be safe or
nonviral DNA are used to help deliver a healthy
gene to the tissue cells.
In general, non-viral vectors are very inefficient at
delivering genes to cardiovascular cells.
Viruses are more effcient but also have a higher
safety risk.
How is gene therapy being used in
cardiovascular disease?
Most gene therapy studies have been done in the
laboratory and the earliest experiments seem
promising for treatment of cardiovascular
disease.
An example of these studies is the use of gene
therapy to help increase blood flow to ischemic
tissue. Ischemia is a condition in which the flow
of blood, and thus oxygen, is restricted to a part
of the body.
Limb ischemia and myocardial ischemia refer to
lack of blood flow and oxygen to the limb and heart
muscle, respectively.
The body’s first response to less blood flow to the
heart is to grow tiny new “collateral” vessels to
help blood flow around the blockage.
(This process is known as angiogenesis.)
For unknown reasons, the process eventually
switches off.
Some proteins in the body can help trigger new
blood vessel growth and so increase the oxygen
supply to the ischemic tissue.
Such angiogenic proteins include the endothelial
growth factors, vascular endothelial growth factor
(VEGF) and fibroblast growth factor (FGF) and
hepatocyte growth factor (HGF).
In gene therapy trials, scientists have used a
variety of different ways to deliver the genes
for VEGF-1, VEGF-2 and FGF4 into the
hearts of patients with advanced myocardial
ischemia.
After gene therapy, patients had less severe
angina (chest pain) and their hearts worked
better.
Similarly, after gene delivery of VEGF to patients
with limb ischemia, the blood supply improved and
leg sores healed better.
Gene therapy has prevented below-knee
amputation in some patients for whom amputation
had been recommended.
Gene therapy has also been successful in preventing
re-occlusion, or re-blockage, of coronary artery
bypass grafts and in keeping arteries open after
angioplasty surgery.
The outlook for gene therapy looks very promising.
However, gene therapy still needs many
improvements before it becomes routine treatment
for cardiovascular disease in the clinic.
Some areas for improvement include selecting
appropriate patient populations for clinical trials,
evaluating side effects, selecting and ensuring the
safety of the genetic material to deliver, and
methods for delivering the gene.