Gene TherapyGene Therapy

Prof. Dr. Marlina, MS, AptProf. Dr. Marlina, MS, Apt

Kuliah I14 Maret 2011

Mata Kuliah: Bioteknologi Mata Kuliah: Bioteknologi FarmasiFarmasi

What is a gene?What is a gene?A gene is a discrete sequence of DNA that A gene is a discrete sequence of DNA that contains information to make a protein. contains information to make a protein. 

Sometimes a gene can be defective or Sometimes a gene can be defective or missing. missing. 

A defective gene may cause a protein that A defective gene may cause a protein that doesn’t work correctly to be made. doesn’t work correctly to be made. 

A missing gene may mean essential A missing gene may mean essential proteins aren’t made.proteins aren’t made.

  What is gene therapy?What is gene therapy?

Gene therapy is correcting functional gene Gene therapy is correcting functional gene loss by delivering genes to human tissues loss by delivering genes to human tissues or simply expression of a "therapeutic or simply expression of a "therapeutic gene" in a target tissue to achieve gene" in a target tissue to achieve benefit.  benefit. 

Often DNA viruses engineered to be safe Often DNA viruses engineered to be safe or nonviral DNA are used to help deliver a or nonviral DNA are used to help deliver a healthy gene to the tissue cells.  healthy gene to the tissue cells. 

In general, non-viral vectors are very In general, non-viral vectors are very inefficient at delivering genes to inefficient at delivering genes to cardiovascular cells. cardiovascular cells.

Viruses are more effcient but also have a Viruses are more effcient but also have a higher safety risk.higher safety risk.

How is gene therapy being used in How is gene therapy being used in

cardiovascular disease?cardiovascular disease?

Most gene therapy studies have been Most gene therapy studies have been done in the laboratory and the earliest done in the laboratory and the earliest experiments seem promising for experiments seem promising for treatment of cardiovascular disease. treatment of cardiovascular disease. 

An example of these studies is the use of An example of these studies is the use of gene therapy to help increase blood flow gene therapy to help increase blood flow to ischemic tissue. Ischemia is a condition to ischemic tissue. Ischemia is a condition in which the flow of blood, and thus in which the flow of blood, and thus oxygen, is restricted to a part of the oxygen, is restricted to a part of the body. body. 

Limb ischemia and myocardial ischemia Limb ischemia and myocardial ischemia refer to lack of blood flow and oxygen to refer to lack of blood flow and oxygen to the limb and heart muscle, respectively. the limb and heart muscle, respectively. 

The body’s first response to less blood flow The body’s first response to less blood flow to the heart is to grow tiny new to the heart is to grow tiny new “collateral” vessels to help blood flow “collateral” vessels to help blood flow around the blockage.  around the blockage.  (This process is known as angiogenesis.) (This process is known as angiogenesis.) 

For unknown reasons, the process For unknown reasons, the process eventually switches off.  eventually switches off. 

Some proteins in the body can help trigger Some proteins in the body can help trigger new blood vessel growth and so increase new blood vessel growth and so increase the oxygen supply to the ischemic tissue.  the oxygen supply to the ischemic tissue. 

Such angiogenic proteins include the Such angiogenic proteins include the endothelial growth factors, vascular endothelial growth factors, vascular endothelial growth factor (VEGF) and endothelial growth factor (VEGF) and fibroblast growth factor (FGF) and fibroblast growth factor (FGF) and hepatocyte growth factor (HGF).hepatocyte growth factor (HGF).    

In gene therapy trials, scientists have In gene therapy trials, scientists have used a variety of different ways to used a variety of different ways to deliver the genes for VEGF-1, VEGF-2 deliver the genes for VEGF-1, VEGF-2 and FGF4 into the hearts of patients and FGF4 into the hearts of patients with advanced myocardial ischemia. with advanced myocardial ischemia. 

After gene therapy, patients had less After gene therapy, patients had less severe angina (chest pain) and their severe angina (chest pain) and their hearts worked better.  hearts worked better. 

Similarly, after gene delivery of VEGF to Similarly, after gene delivery of VEGF to patients with limb ischemia, the blood patients with limb ischemia, the blood supply improved and leg sores healed supply improved and leg sores healed better.  better.  

Gene therapy has prevented below-knee Gene therapy has prevented below-knee amputation in some patients for whom amputation in some patients for whom amputation had been recommended.amputation had been recommended.

Gene therapy has also been successful in Gene therapy has also been successful in preventing re-occlusion, or re-blockage, of preventing re-occlusion, or re-blockage, of coronary artery bypass grafts and in coronary artery bypass grafts and in keeping arteries open after angioplasty keeping arteries open after angioplasty surgery.surgery.

The outlook for gene therapy looks very The outlook for gene therapy looks very promising. promising. 

However, gene therapy still needs many However, gene therapy still needs many improvements before it becomes routine improvements before it becomes routine treatment for cardiovascular disease in the treatment for cardiovascular disease in the clinic.  clinic. 

Some areas for improvement include selecting Some areas for improvement include selecting appropriate patient populations for clinical appropriate patient populations for clinical trials, evaluating side effects, selecting and trials, evaluating side effects, selecting and ensuring the safety of the genetic material to ensuring the safety of the genetic material to deliver, and methods for delivering the gene.deliver, and methods for delivering the gene.