Fact Sheet 7.18

Overview
  • Gene therapy is an experimental treatment that involves introducing genetic material into a person’s cells to fight disease.
  • Researchers are studying gene therapy for cancer through a number of different approaches.
  • A gene can be delivered to a cell using a carrier known as a “vector.” The most common types of vectors used in gene therapy are viruses.
  • The viruses used in gene therapy are altered to make them safe; however, some risks still exist with gene therapy.
  • A clinical trial using gene therapy must be approved by at least two review boards at the scientists’ institution, as well as the U.S. Food and Drug Administration and the National Institutes of Health Recombinant DNA Advisory Committee.
  • The Ethical, Legal, and Social Implications Program was established in 1990 to identify, analyze, and address the implications of human genetics research.

  1. What are genes?
  2. Genes are the biological units of heredity. Genes determine obvious traits, such as hair and eye color, as well as more subtle characteristics, such as the ability of the blood to carry oxygen. Complex characteristics, such as physical strength, may be shaped by the interaction of a number of different genes along with environmental influences.

    A gene is part of a deoxyribonucleic acid molecule. Humans have between 50,000 and 100,000 genes. Genes carry instructions that allow the cells to produce specific proteins such as enzymes. During the creation of proteins, cells use another molecule, ribonucleic acid, to translate the genetic information stored in DNA.

    Only certain genes in a cell are active at any given moment. As cells mature, many genes become permanently inactive. The pattern of active and inactive genes in a cell and the resulting protein composition determine what kind of cell it is and what it can and cannot do. Flaws in genes can result in disease.

  3. What is gene therapy?
  4. Advances in understanding and manipulating genes have set the stage for scientists to alter patients’ genetic material to fight or prevent disease. Gene therapy is an experimental treatment that involves introducing genetic material into a person’s cells to fight disease. Gene therapy is being studied in clinical trials for many different types of cancer and for other diseases. It is not currently available outside a clinical trial.

  5. How is gene therapy being studied in the treatment of cancer?
  6. Researchers are studying several ways to treat cancer using gene therapy. Some approaches target healthy cells to enhance their ability to fight cancer. Other approaches target cancer cells, to destroy them or prevent their growth. Some gene therapy techniques under study are described below.

  7. How are genes transferred into cells so that gene therapy can take place?
  8. In general, a gene cannot be directly inserted into a person’s cell. It must be delivered to the cell using a carrier, or “vector.” The vectors most commonly used in gene therapy are viruses. Viruses have a unique ability to recognize certain cells and insert their DNA into the cells.

    In some gene therapy clinical trials, cells from the patient’s blood or bone marrow are removed and grown in the laboratory. The cells are exposed to the virus that is carrying the desired gene. The virus enters the cells and inserts the desired gene into the cells’ DNA. The cells grow in the laboratory and are then returned to the patient by injection into a vein. This type of gene therapy is called ex vivo because the cells are grown outside the body. The gene is transferred into the patient’s cells while the cells are outside the patient’s body.

    In other studies, vectors or liposomes are used to deliver the desired gene to cells in the patient’s body. This form of gene therapy is called in vivo, because the gene is transferred to cells inside the patient’s body.

  9. What types of viruses are used in gene therapy, and how can they be used safely?
  10. Many gene therapy clinical trials rely on retroviruses to deliver the desired gene. Other viruses used as vectors include adenoviruses, adeno-associated viruses, lentiviruses, poxviruses, and herpes viruses. These viruses differ in how well they transfer the genes to cells, which cells they can recognize and infect, and whether they alter the cell’s DNA permanently or temporarily. Thus, researchers may use different vectors, depending on the specific characteristics and requirements of the study.

    Scientists alter the viruses used in gene therapy to make them safe for humans and to increase their ability to deliver specific genes to a patient’s cells. Depending on the type of virus and the goals of the research study, scientists may inactivate certain genes in the viruses to prevent them from reproducing or causing disease. Researchers may also alter the virus so that it better recognizes and enters the target cell.

  11. What risks are associated with current gene therapy trials?
  12. Viruses can usually infect more than one type of cell. Thus, when viral vectors are used to carry genes into the body, they might infect healthy cells as well as cancer cells. Another danger is that the new gene might be inserted in the wrong location in the DNA, possibly causing cancer or other harmful mutations to the DNA.

    In addition, when viruses or liposomes are used to deliver DNA to cells inside the patient’s body, there is a slight chance that this DNA could unintentionally be introduced into the patient’s reproductive cells. If this happens, it could produce changes that may be passed on if a patient has children after treatment.

    Other concerns include the possibility that transferred genes could be “overexpressed,” producing so much of the missing protein as to be harmful; that the viral vector could cause inflammation or an immune reaction; and that the virus could be transmitted from the patient to other individuals or into the environment.

    Scientists use animal testing and other precautions to identify and avoid these risks before any clinical trials are conducted in humans.

  13. What major problems must scientists overcome before gene therapy becomes a common technique for treating disease?
  14. Scientists need to identify more efficient ways to deliver genes to the body. To treat cancer and other diseases effectively with gene therapy, researchers must develop vectors that can be injected into the patient and specifically focus on the target cells located throughout the body. More work is also needed to ensure that the vectors will successfully insert the desired genes into each of these target cells.

    Researchers also need to be able to deliver genes consistently to a precise location in the patient’s DNA, and ensure that transplanted genes are precisely controlled by the body’s normal physiologic signals.

    Although scientists are working hard on these problems, it is impossible to predict when they will have effective solutions.

  15. The first disease approved for treatment with gene therapy was adenosine deaminase deficiency. What is this disease and why was it selected?
  16. ADA deficiency is a rare genetic disease. The normal ADA gene produces an enzyme called adenosine deaminase, which is essential to the body’s immune system. Patients with this condition do not have normal ADA genes and do not produce functional ADA enzyme. ADA-deficient children are born with severe immunodeficiency and are prone to repeated serious infections, which may be life-threatening. Although ADA deficiency can be treated with a drug called PEG-ADA, the drug is expensive and must be taken for life by injection into a vein.

    ADA deficiency was selected for the first approved human gene therapy trial for several reasons:

  17. How do gene therapy trials receive approval?
  18. A proposed gene therapy trial, or protocol, must be approved by at least two review boards at the scientists’ institution. Gene therapy protocols must also be approved by the U.S. Food and Drug Administration, which regulates all gene therapy products. In addition, trials that are funded by the National Institutes of Health must be registered with the NIH Recombinant DNA Advisory Committee. The NIH, which includes more than 20 institutes and offices, is the Federal focal point for biomedical research in the United States.

  19. Why are there so many steps in this process?
  20. Any studies involving humans must be reviewed with great care. Gene therapy in particular is a potentially very powerful technique, is relatively new, and could have profound implications. These factors make it necessary for scientists to take special precautions with gene therapy.

  21. What are some of the social and ethical issues surrounding human gene therapy?
  22. In large measure, the issues are the same as those faced whenever a powerful new technology is developed. Such technologies can accomplish great good, but they can also result in great harm if applied unwisely.

    Gene therapy is currently focused on correcting genetic flaws and curing life-threatening disease, and regulations are in place for conducting these types of studies. But in the future, when the techniques of gene therapy have become simpler and more accessible, society will need to deal with more complex questions.

    One such question is related to the possibility of genetically altering human eggs or sperm, the reproductive cells that pass genes on to future generations. Another question is related to the potential for enhancing human capabilities—for example, improving memory and intelligence—by genetic intervention. Although both germ-line gene therapy and genetic enhancement have the potential to produce benefits, possible problems with these procedures worry many scientists.

    Germ-line gene therapy would forever change the genetic make-up of an individual’s descendants. Thus, the human gene pool would be permanently affected. Although these changes would presumably be for the better, an error in technology or judgment could have far-reaching consequences. The NIH does not approve germ-line gene therapy in humans.

    In the case of genetic enhancement, there is concern that such manipulation could become a luxury available only to the rich and powerful. Some also fear that widespread use of this technology could lead to new definitions of “normal” that would exclude individuals who are, for example, of merely average intelligence. And, justly or not, some people associate all genetic manipulation with past abuses of the concept of “eugenics,” or the study of methods of improving genetic qualities through selective breeding.

  23. What is being done to address these social and ethical issues?
  24. Scientists working on the Human Genome Project, which has completed mapping and sequencing all of the genes in humans, have recognized that the information gained from this work will have profound implications for individuals, families, and society. The Ethical, Legal, and Social Implications Program was established in 1990 to address these issues. The ELSI Program is designed to identify, analyze, and address the ethical, legal, and social implications of human genetics research at the same time that the basic scientific issues are being studied. In this way, problem areas can be identified and solutions developed before the scientific information becomes part of standard health care practice. More information about the HGP and the ELSI Program can be found on the National Human Genome Research Institute Web site at http://www.genome.gov on the Internet.

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