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What is Gene Therapy

Gene therapy is an experimental treatment that involves introducing genetic material into a person’s cells to fight or prevent disease. Researchers are studying gene therapy for a number of diseases, such as severe combined immuno-deficiencies, hemophilia, Parkinson's disease, cancer and even HIV, through a number of different approaches (see video: 'Gene Therapy a new tool to cure human diseases'). 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, although some risks still exist with gene therapy. The technology is still in its infancy, but it has been used with some success.

Basic Process of Gene Therapy

Several approaches to gene therapy are being tested, including:
    - Replacing a mutated gene that causes disease with a healthy copy of the gene
    - Inactivating, or “knocking out,” a mutated gene that is functioning improperly
    - Introducing a new gene into the body to help fight a disease

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. Vector systems can be divided into:

  Viral Vectors
  Non-viral Vectors


Currently, the most common type of vectors are viruses that have been genetically altered to carry normal human DNA (see also Wiley database on vectors used in gene therapy trials). Viruses have evolved a way of encapsulating and delivering their genes to human cells in a pathogenic manner. Scientists have tried to harness this ability by manipulating the viral genome to remove disease-causing genes and insert therapeutic ones (see also video 2).

Target cells such as the patient's liver or lung cells are infected with the vector. The vector then unloads its genetic material containing the therapeutic human gene into the target cell. The generation of a functional protein product from the therapeutic gene restores the target cell to a normal state.

Video 1: Lecture, What is Gene Therapy
(YouTube, 10:01)
Video 2: What is Recombinant DNA
(YouTube, 4:35)

Types of Gene Therapy

Virtually all cells in the human body contain genes, making them potential targets for gene therapy. However, these cells can be divided into two major categories: somatic cells (most cells of the body) or cells of the germline (eggs or sperm). In theory it is possible to transform either somatic cells or germ cells.

Gene therapy using germ line cells results in permanent changes that are passed down to subsequent generations. If done early in embryologic development, such as during preimplantation diagnosis and in vitro fertilization, the gene transfer could also occur in all cells of the developing embryo. The appeal of germ line gene therapy is its potential for offering a permanent therapeutic effect for all who inherit the target gene. Successful germ line therapies introduce the possibility of eliminating some diseases from a particular family, and ultimately from the population, forever. However, this also raises controversy. Some people view this type of therapy as unnatural, and liken it to "playing God." Others have concerns about the technical aspects. They worry that the genetic change propagated by germ line gene therapy may actually be deleterious and harmful, with the potential for unforeseen negative effects on future generations.

Somatic cells are nonreproductive. Somatic cell therapy is viewed as a more conservative, safer approach because it affects only the targeted cells in the patient, and is not passed on to future generations. In other words, the therapeutic effect ends with the individual who receives the therapy. However, this type of therapy presents unique problems of its own. Often the effects of somatic cell therapy are short-lived. Because the cells of most tissues ultimately die and are replaced by new cells, repeated treatments over the course of the individual's life span are required to maintain the therapeutic effect. Transporting the gene to the target cells or tissue is also problematic. Regardless of these difficulties, however, somatic cell gene therapy is appropriate and acceptable for many disorders, including cystic fibrosis, muscular dystrophy, cancer, and certain infectious diseases. Clinicians can even perform this therapy in utero, potentially correcting or treating a life-threatening disorder that may significantly impair a baby's health or development if not treated before birth.

In summary, the distinction is that the results of any somatic gene therapy are restricted to the actual patient and are not passed on to his or her children. All gene therapy to date on humans has been directed at somatic cells, whereas germline engineering in humans remains controversial and prohibited in for instance the European Union.

Somatic gene therapy can be broadly split into two categories:

ex vivo, which means exterior (where cells are modified outside the body and then transplanted back in again). 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 treated outside the body.
in vivo, which means interior (where genes are changed in cells still in the body). This form of gene therapy is called in vivo, because the gene is transferred to cells inside the patient’s body.

Gene Doping

Gene therapy for restoring muscle lost to age or disease is poised to enter the clinic, but athletes are eyeing it to enhance performance. The non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance is defined as Gene Doping by the World Anti-Doping Agency (WADA).

A complex ethical and philosophical issue is what defines gene doping, especially in the context of bioethical debates about human enhancement. Gene doping could involve the recreational use of gene therapies intended to treat muscle-wasting disorders. Many of these chemicals may be indistinguishable from their natural counterparts. In such cases, nothing unusual would enter the bloodstream so officials would detect nothing in a blood or urine test. For example, gene doping could be used to provide athletes a source of erythropoietin (EPO), a hormone that promotes the formation of red blood cells that is already widely abused in sports. Another candidate gene is Insulin-like Growth Factor 1 (IGF-1) which partly controls the building and repair of muscles by stimulating the proliferation of satellite cells. See also Gene Doping article by Prof. H. Lee Sweeney.

The historical development of policy associated with gene doping began in 2001 when the International Olympic Committee (IOC) Medical Commission met to discuss the implications of gene therapy for sport. It was shortly followed by the WADA, which met in 2002 to discuss genetic enhancement. In 2003, WADA decided to include a prohibition of gene doping within their World Anti-Doping Code, which is formalized in its 2004 World Anti-Doping Code. In 2004, the Netherlands Centre for Doping Affairs (NeCeDo) and the WADA have organized a “Gene Doping” workshop. In addition, NeCeDo has published a report on gene doping as an inventory of the possible applications and risks of genetic manipulation in sports. Although there have been no documented cases of gene doping, the science of gene therapy and interest in the techniques by the sports community has risen to a level that makes gene doping inevitable.

The World Anti-Doping Agency (WADA) has already asked scientists to help find ways to prevent gene therapy from becoming the newest means of doping. In December 2005, the World Anti-Doping Agency hosted its second landmark meeting on gene doping, which took place in Stockholm. At this meeting, the delegates drafted a declaration on gene doping which, for the first time, included a strong discouragement of the use of genetic testing for performance. Recently, German scientists from Tübingen and Mainz have developed a blood test that can reliably detect gene doping even after 56 days: "For the first time, a direct method is now available that uses conventional blood samples to detect doping via gene transfer". See news item: Gene Doping Detectable With a Simple Blood Test.

Analogous to gene doping, non-therapeutic applications of gene therapy can be envisaged in animals for the purpose of growth stimulation and improved meat production (see also Belgian Blue Bull), for example by growth hormone, myostatin and anabolic hormones. Gene doping to improve sport performance is not limited to humans, but has also interest in for example the sport of horse racing.

Video 3: Gene Doping - Part 1
(YouTube, 7:37)
Video 4: Gene Doping - Part 2
(YouTube, 5:15)