1. Gene Therapy Prof. Dr. Marlina, MS, Apt Kuliah I 14 Maret 2011 Mata Kuliah: Bioteknologi Farmasi

2. What is a gene? A gene is a discrete sequence of DNA that contains information to make a protein. A gene is a discrete sequence of DNA that contains information to make a protein. Sometimes a gene can be defective or missing. Sometimes a gene can be defective or missing. A defective gene may cause a protein that doesn’t work correctly to be made. 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. A missing gene may mean essential proteins aren’t made.

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

4. 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.

5. 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. 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. 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.

6. Limb ischemia and myocardial ischemia refer to lack of blood flow and oxygen to the limb and heart muscle, respectively. 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. 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.) (This process is known as angiogenesis.) For unknown reasons, the process eventually switches off. For unknown reasons, the process eventually switches off.

7. Some proteins in the body can help trigger new blood vessel growth and so increase the oxygen supply to the ischemic tissue. 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). Such angiogenic proteins include the endothelial growth factors, vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) and hepatocyte growth factor (HGF).

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

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

10. 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.

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