gene therapy

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Gene Therapy

 Gene therapy is a rapidly growing field of medicine in which genes are introduced into the body to treat diseases. Genes control heredity and provide the basic biological code for determining a cell's specific functions. Gene therapy seeks to provide genes that correct or supplant the disease-controlling functions of cells that are not, in essence, doing their job. Somatic gene therapy introduces therapeutic genes at the tissue or cellular level to treat a specific individual. Germ-line gene therapy inserts genes into reproductive cells or possibly into embryos to correct genetic defects that could be passed on to future generations. Initially conceived as an approach for treating inherited diseases, like cystic fibrosis and Huntington's disease, the scope of potential gene therapies has grown to include treatments for cancers, arthritis, and infectious diseases. Although gene therapy testing in humans has advanced rapidly, many questions surround its use. For example, some scientists are concerned that the therapeutic genes themselves may cause disease. Others fear that germ-line gene therapy may be used to control human development in ways not connected with disease, like intelligence or appearance.

The biological basis of gene therapy

Gene therapy has grown out of the science of genetics or how heredity works. Scientists know that life begins in a cell, the basic building block of all multicellular organisms. Humans, for instance, are made up of trillions of cells, each performing a specific function. Within the cell's nucleus (the center part of a cell that regulates its chemical functions) are pairs of chromosomes. These threadlike structures are made up of a single molecule of DNA (deoxyribonucleic acid), which carries the blueprint of life in the form of codes, or genes, that determine inherited characteristics.
A DNA molecule looks like two ladders with one of the sides taken off both and then twisted around each other. The rungs of these ladders meet (resulting in a spiral staircase-like structure) and are called base pairs. Base pairs are made up of nitrogen molecules and arranged in specific sequences. Millions of these base pairs, or sequences, can make up a single gene, specifically defined as a segment of the chromosome and DNA that contains certain hereditary information. The gene, or combination of genes formed by these base pairs ultimately direct an organism's growth and characteristics through the production of certain chemicals, primarily proteins, which carry out most of the body's chemical functions and biological reactions.
Scientists have long known that alterations in genes present within cells can cause inherited diseases like cystic fibrosis, sickle-cell anemia, and hemophilia. Similarly, errors in the total number of chromosomes can cause conditions such as Down syndrome or Turner's syndrome. As the study of genetics advanced, however, scientists learned that an altered genetic sequence also can make people more susceptible to diseases, like atherosclerosis, cancer, and even schizophrenia. These diseases have a genetic component, but also are influenced by environmental factors (like diet and lifestyle). The objective of gene therapy is to treat diseases by introducing functional genes into the body to alter the cells involved in the disease process by either replacing missing genes or providing copies of functioning genes to replace nonfunctioning ones. The inserted genes can be naturally-occurring genes that produce the desired effect or may be genetically engineered (or altered) genes.
Scientists have known how to manipulate a gene's structure in the laboratory since the early 1970s through a process called gene splicing. The process involves removing a fragment of DNA containing the specific genetic sequence desired, then inserting it into the DNA of another gene. The resultant product is called recombinant DNA and the process is genetic engineering.
There are basically two types of gene therapy. Germ-line gene therapy introduces genes into reproductive cells (sperm and eggs) or someday possibly into embryos in hopes of correcting genetic abnormalities that could be passed on to future generations. Most of the current work in applying gene therapy, however, has been in the realm of somatic gene therapy. In this type of gene therapy, therapeutic genes are inserted into tissue or cells to produce a naturally occurring protein or substance that is lacking or not functioning correctly in an individual patient.

Viral vectors

In both types of therapy, scientists need something to transport either the entire gene or a recombinant DNA to the cell's nucleus, where the chromosomes and DNA reside. In essence, vectors are molecular delivery trucks. One of the first and most popular vectors developed were viruses because they invade cells as part of the natural infection process. Viruses have the potential to be excellent vectors because they have a specific relationship with the host in that they colonize certain cell types and tissues in specific organs. As a result, vectors are chosen according to their attraction to certain cells and areas of the body.
One of the first vectors used was retroviruses. Because these viruses are easily cloned (artificially reproduced) in the laboratory, scientists have studied them extensively and learned a great deal about their biological action. They also have learned how to remove the genetic information that governs viral replication, thus reducing the chances of infection.
Retroviruses work best in actively dividing cells, but cells in the body are relatively stable and do not divide often. As a result, these cells are used primarily for ex vivo (outside the body) manipulation. First, the cells are removed from the patient's body, and the virus, or vector, carrying the gene is inserted into them. Next, the cells are placed into a nutrient culture where they grow and replicate. Once enough cells are gathered, they are returned to the body, usually by injection into the blood stream. Theoretically, as long as these cells survive, they will provide the desired therapy.
Another class of viruses, called the adenoviruses, also may prove to be good gene vectors. These viruses can effectively infect nondividing cells in the body, where the desired gene product then is expressed naturally. In addition to being a more efficient approach to gene transportation, these viruses, which cause respiratory infections, are more easily purified and made stable than retroviruses, resulting in less chance of an unwanted viral infection. However, these viruses live for several days in the body, and some concern surrounds the possibility of infecting others with the viruses through sneezing or coughing. Other viral vectors include influenza viruses, Sindbis virus, and a herpes virus that infects nerve cells.
Scientists also have delved into nonviral vectors. These vectors rely on the natural biological process in which cells uptake (or gather) macromolecules. One approach is to use liposomes, globules of fat produced by the body and taken up by cells. Scientists also are investigating the introduction of raw recombinant DNA by injecting it into the bloodstream or placing it on microscopic beads of gold shot into the skin with a "gene-gun." Another possible vector under development is based on dendrimer molecules. A class of polymers (naturally occurring or artificial substances that have a high molecular weight and formed by smaller molecules of the same or similar substances), is "constructed" in the laboratory by combining these smaller molecules. They have been used in manufacturing Styrofoam, polyethylene cartons, and Plexiglass. In the laboratory, dendrimers have shown the ability to transport genetic material into human cells. They also can be designed to form an affinity for particular cell membranes by attaching to certain sugars and protein groups.

The history of gene therapy

In the early 1970s, scientists proposed "gene surgery" for treating inherited diseases caused by faulty genes. The idea was to take out the disease-causing gene and surgically implant a gene that functioned properly. Although sound in theory, scientists, then and now, lack the biological knowledge or technical expertise needed to perform such a precise surgery in the human body.
However, in 1983, a group of scientists from Baylor College of Medicine in Houston, Texas, proposed that gene therapy could one day be a viable approach for treating Lesch-Nyhan disease, a rare neurological disorder. The scientists conducted experiments in which an enzyme-producing gene (a specific type of protein) for correcting the disease was injected into a group of cells for replication. The scientists theorized the cells could then be injected into people with Lesch-Nyhan disease, thus correcting the genetic defect that caused the disease.
As the science of genetics advanced throughout the 1980s, gene therapy gained an established foothold in the minds of medical scientists as a promising approach to treatments for specific diseases. One of the major reasons for the growth of gene therapy was scientists' increasing ability to identify the specific genetic malfunctions that caused inherited diseases. Interest grew as further studies of DNA and chromosomes (where genes reside) showed that specific genetic abnormalities in one or more genes occurred in successive generations of certain family members who suffered from diseases like intestinal cancer, bipolar disorder, Alzheimer's disease, heart disease, diabetes, and many more. Although the genes may not be the only cause of the disease in all cases, they may make certain individuals more susceptible to developing the disease because of environmental influences, like smoking, pollution, and stress. In fact, some scientists theorize that all diseases may have a genetic component.
On September 14, 1990, a four-year old girl suffering from a genetic disorder that prevented her body from producing a crucial enzyme became the first person to undergo gene therapy in the United States. Because her body could not produce adenosine deaminase (ADA), she had a weakened immune system, making her extremely susceptible to severe, life-threatening infections. W. French Anderson and colleagues at the National Institutes of Health's Clinical Center in Bethesda, Maryland, took white blood cells (which are crucial to proper immune system functioning) from the girl, inserted ADA producing genes into them, and then transfused the cells back into the patient. Although the young girl continued to show an increased ability to produce ADA, debate arose as to whether the improvement resulted from the gene therapy or from an additional drug treatment she received.
Nevertheless, a new era of gene therapy began as more and more scientists sought to conduct clinical trial (testing in humans) research in this area. In that same year, gene therapy was tested on patients suffering from melanoma (skin cancer). The goal was to help them produce antibodies (disease fighting substances in the immune system) to battle the cancer.
These experiments have spawned an ever growing number of attempts at gene therapies designed to perform a variety of functions in the body. For example, a gene therapy for cystic fibrosis aims to supply a gene that alters cells, enabling them to produce a specific protein to battle the disease. Another approach was used for brain cancer patients, in which the inserted gene was designed to make the cancer cells more likely to respond to drug treatment. Another gene therapy approach for patients suffering from artery blockage, which can lead to strokes, induces the growth of new blood vessels near clogged arteries, thus ensuring normal blood circulation.
Currently, there are a host of new gene therapy agents in clinical trials. In the United States, both nucleic acid based (in vivo) treatments and cell-based (ex vivo) treatments are being investigated. Nucleic acid based gene therapy uses vectors (like viruses) to deliver modified genes to target cells. Cell-based gene therapy techniques remove cells from the patient in order to genetically alter them then reintroduce them to the patient's body. Presently, gene therapies for the following diseases are being developed: cystic fibrosis (using adenoviral vector), HIV infection (cell-based), malignant melanoma (cell-based), Duchenne muscular dystrophy (cell-based), hemophilia B (cell-based), kidney cancer (cell-based), Gaucher's Disease (retroviral vector), breast cancer (retroviral vector), and lung cancer (retroviral vector). When a cell or individual is treated using gene therapy and successful incorporation of engineered genes has occurred, the cell or individual is said to be transgenic.
The medical establishment's contribution to transgenic research has been supported by increased government funding. In 1991, the U.S. government provided $58 million for gene therapy research, with increases in funding of $15-40 million dollars a year over the following four years. With fierce competition over the promise of societal benefit in addition to huge profits, large pharmaceutical corporations have moved to the forefront of transgenic research. In an effort to be first in developing new therapies, and armed with billions of dollars of research funds, such corporations are making impressive strides toward making gene therapy a viable reality in the treatment of once elusive diseases.

Diseases targeted for treatment by gene therapy

The potential scope of gene therapy is enormous. More than 4,200 diseases have been identified as resulting directly from abnormal genes, and countless others that may be partially influenced by a person's genetic makeup. Initial research has concentrated on developing gene therapies for diseases whose genetic origins have been established and for other diseases that can be cured or improved by substances genes produce.
The following are examples of potential gene therapies. People suffering from cystic fibrosis lack a gene needed to produce a salt-regulating protein. This protein regulates the flow of chloride into epithelial cells, (the cells that line the inner and outer skin layers) that cover the air passages of the nose and lungs. Without this regulation, patients with cystic fibrosis build up a thick mucus that makes them prone to lung infections. A gene therapy technique to correct this abnormality might employ an adenovirus to transfer a normal copy of what scientists call the cystic fibrosis transmembrane conductance regulator, or CTRF, gene. The gene is introduced into the patient by spraying it into the nose or lungs. Researchers announced in 2004 that they had, for the first time, treated a dominant neurogenerative disease called Spinocerebella ataxia type 1, with gene therapy. This could lead to treating similar diseases such as Huntingtons disease. They also announced a single intravenous injection could deliver therapy to all muscles, perhaps providing hope to people with muscular dystrophy.
Familial hypercholesterolemia (FH) also is an inherited disease, resulting in the inability to process cholesterol properly, which leads to high levels of artery-clogging fat in the blood stream. Patients with FH often suffer heart attacks and strokes because of blocked arteries. A gene therapy approach used to battle FH is much more intricate than most gene therapies because it involves partial surgical removal of patients' livers (ex vivo transgene therapy). Corrected copies of a gene that serve to reduce cholesterol build-up are inserted into the liver sections, which then are transplanted back into the patients.
Gene therapy also has been tested on patients with AIDS. AIDS is caused by the human immunodeficiency virus (HIV), which weakens the body's immune system to the point that sufferers are unable to fight off diseases like pneumonias and cancer. In one approach, genes that produce specific HIV proteins have been altered to stimulate immune system functioning without causing the negative effects that a complete HIV molecule has on the immune system. These genes are then injected in the patient's blood stream. Another approach to treating AIDS is to insert, via white blood cells, genes that have been genetically engineered to produce a receptor that would attract HIV and reduce its chances of replicating. In 2004, researchers reported that had developed a new vaccine concept for HIV, but the details were still in development.
Several cancers also have the potential to be treated with gene therapy. A therapy tested for melanoma, or skin cancer, involves introducing a gene with an anticancer protein called tumor necrosis factor (TNF) into test tube samples of the patient's own cancer cells, which are then reintroduced into the patient. In brain cancer, the approach is to insert a specific gene that increases the cancer cells' susceptibility to a common drug used in fighting the disease. In 2003, researchers reported that they had harnessed the cell killing properties of adenoviruses to treat prostate cancer. A 2004 report said that researchers had developed a new DNA vaccine that targeted the proteins expressed in cervical cancer cells.
Gaucher disease is an inherited disease caused by a mutant gene that inhibits the production of an enzyme called glucocerebrosidase. Patients with Gaucher disease have enlarged livers and spleens and eventually their bones deteriorate. Clinical gene therapy trials focus on inserting the gene for producing this enzyme.
Gene therapy also is being considered as an approach to solving a problem associated with a surgical procedure known as balloon angioplasty. In this procedure, a stent (in this case, a type of tubular scaffolding) is used to open the clogged artery. However, in response to the trauma of the stent insertion, the body initiates a natural healing process that produces too many cells in the artery and results in restenosis, or reclosing of the artery. The gene therapy approach to preventing this unwanted side effect is to cover the outside of the stents with a soluble gel. This gel contains vectors for genes that reduce this overactive healing response.
Regularly throughout the past decade, and no doubt over future years, scientists have and will come up with new possible ways for gene therapy to help treat human disease. Recent advancements include the possibility of reversing hearing loss in humans with experimental growing of new sensory cells in adult guinea pigs, and avoiding amputation in patients with severe circulatory problems in their legs with angiogenic growth factors.

The human genome project

Although great strides have been made in gene therapy in a relatively short time, its potential usefulness has been limited by lack of scientific data concerning the multitude of functions that genes control in the human body. For instance, it is now known that the vast majority of genetic material does not store information for the creation of proteins, but rather is involved in the control and regulation of gene expression, and is, thus, much more difficult to interpret. Even so, each individual cell in the body carries thousands of genes coding for proteins, with some estimates as high as 150,000 genes. For gene therapy to advance to its full potential, scientists must discover the biological role of each of these individual genes and where the base pairs that make them up are located on DNA.
To address this issue, the National Institutes of Health initiated the Human Genome Project in 1990. Led by James D. Watson (one of the co-discoverers of the chemical makeup of DNA) the project's 15-year goal is to map the entire human genome (a combination of the words gene and chromosomes). A genome map would clearly identify the location of all genes as well as the more than three billion base pairs that make them up. With a precise knowledge of gene locations and functions, scientists may one day be able to conquer or control diseases that have plagued humanity for centuries.
Scientists participating in the Human Genome Project identified an average of one new gene a day, but many expected this rate of discovery to increase. By the year 2005, their goal was to determine the exact location of all the genes on human DNA and the exact sequence of the base pairs that make them up. Some of the genes identified through this project include a gene that predisposes people to obesity, one associated with programmed cell death (apoptosis), a gene that guides HIV viral reproduction, and the genes of inherited disorders like Huntington's disease, Lou Gehrig's disease, and some colon and breast cancers. In April 2003, the finished sequence was announced, with 99% of the human genome's gene-containing regions mapped to an accuracy of 99.9%.

The future of gene therapy

Gene therapy seems elegantly simple in its concept: supply the human body with a gene that can correct a biological malfunction that causes a disease. However, there are many obstacles and some distinct questions concerning the viability of gene therapy. For example, viral vectors must be carefully controlled lest they infect the patient with a viral disease. Some vectors, like retroviruses, also can enter cells functioning properly and interfere with the natural biological processes, possibly leading to other diseases. Other viral vectors, like the adenoviruses, often are recognized and destroyed by the immune system so their therapeutic effects are short-lived. Maintaining gene expression so it performs its role properly after vector delivery is difficult. As a result, some therapies need to be repeated often to provide long-lasting benefits.
One of the most pressing issues, however, is gene regulation. Genes work in concert to regulate their functioning. In other words, several genes may play a part in turning other genes on and off. For example, certain genes work together to stimulate cell division and growth, but if these are not regulated, the inserted genes could cause tumor formation and cancer. Another difficulty is learning how to make the gene go into action only when needed. For the best and safest therapeutic effort, a specific gene should turn on, for example, when certain levels of a protein or enzyme are low and must be replaced. But the gene also should remain dormant when not needed to ensure it doesn't oversupply a substance and disturb the body's delicate chemical makeup.
One approach to gene regulation is to attach other genes that detect certain biological activities and then react as a type of automatic off-and-on switch that regulates the activity of the other genes according to biological cues. Although still in the rudimentary stages, researchers are making headway in inhibiting some gene functioning by using a synthetic DNA to block gene transcriptions (the copying of genetic information). This approach may have implications for gene therapy.

The ethics of gene therapy

While gene therapy holds promise as a revolutionary approach to treating disease, ethical concerns over its use and ramifications have been expressed by scientists and lay people alike. For example, since much needs to be learned about how these genes actually work and their long-term effect, is it ethical to test these therapies on humans, where they could have a disastrous result? As with most clinical trials concerning new therapies, including many drugs, the patients participating in these studies usually have not responded to more established therapies and often are so ill the novel therapy is their only hope for long-term survival.
Another questionable outgrowth of gene therapy is that scientists could possibly manipulate genes to genetically control traits in human offspring that are not health related. For example, perhaps a gene could be inserted to ensure that a child would not be bald, a seemingly harmless goal. However, what if genetic manipulation was used to alter skin color, prevent homosexuality, or ensure good looks? If a gene is found that can enhance intelligence of children who are not yet born, will everyone in society, the rich and the poor, have access to the technology or will it be so expensive only the elite can afford it?
The Human Genome Project, which plays such an integral role for the future of gene therapy, also has social repercussions. If individual genetic codes can be determined, will such information be used against people? For example, will someone more susceptible to a disease have to pay higher insurance premiums or be denied health insurance altogether? Will employers discriminate between two potential employees, one with a "healthy" genome and the other with genetic abnormalities?
Some of these concerns can be traced back to the eugenics movement popular in the first half of the twentieth century. This genetic "philosophy" was a societal movement that encouraged people with "positive" traits to reproduce while those with less desirable traits were sanctioned from having children. Eugenics was used to pass strict immigration laws in the United States, barring less suitable people from entering the country lest they reduce the quality of the country's collective gene pool. Probably the most notorious example of eugenics in action was the rise of Nazism in Germany, which resulted in the Eugenic Sterilization Law of 1933. The law required sterilization for those suffering from certain disabilities and even for some who were simply deemed "ugly." To ensure that this novel science is not abused, many governments have established organizations specifically for overseeing the development of gene therapy. In the United States, the Food and Drug Administration (FDA) and the National Institutes of Health require scientists to take a precise series of steps and meet stringent requirements before proceeding with clinical trials. As of mid-2004, more than 300 companies were carrying out gene medicine developments and 500 clinical trials were underway. How to deliver the therapy is the key to unlocking many of the researchers discoveries.
In fact, gene therapy has been immersed in more controversy and surrounded by more scrutiny in both the health and ethical arena than most other technologies (except, perhaps, for cloning) that promise to substantially change society. Despite the health and ethical questions surrounding gene therapy, the field will continue to grow and is likely to change medicine faster than any previous medical advancement.

Key terms

Cell — The smallest living unit of the body that groups together to form tissues and help the body perform specific functions.
Chromosome — A microscopic thread-like structure found within each cell of the body, consisting of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Changes in either the total number of chromosomes or their shape and size (structure) may lead to physical or mental abnormalities.
Clinical trial — The testing of a drug or some other type of therapy in a specific population of patients.
Clone — A cell or organism derived through asexual (without sex) reproduction containing the identical genetic information of the parent cell or organism.
Deoxyribonucleic acid (DNA) — The genetic material in cells that holds the inherited instructions for growth, development, and cellular functioning.
Embryo — The earliest stage of development of a human infant, usually used to refer to the first eight weeks of pregnancy. The term fetus is used from roughly the third month of pregnancy until delivery.
Enzyme — A protein that causes a biochemical reaction or change without changing its own structure or function.
Eugenics — A social movement in which the population of a society, country, or the world is to be improved by controlling the passing on of hereditary information through mating.
Gene — A building block of inheritance, which contains the instructions for the production of a particular protein, and is made up of a molecular sequence found on a section of DNA. Each gene is found on a precise location on a chromosome.
Gene transcription — The process by which genetic information is copied from DNA to RNA, resulting in a specific protein formation.
Genetic engineering — The manipulation of genetic material to produce specific results in an organism.
Genetics — The study of hereditary traits passed on through the genes.
Germ-line gene therapy — The introduction of genes into reproductive cells or embryos to correct inherited genetic defects that can cause disease.
Liposome — Fat molecule made up of layers of lipids.
Macromolecules — A large molecule composed of thousands of atoms.
Nitrogen — A gaseous element that makes up the base pairs in DNA.
Nucleus — The central part of a cell that contains most of its genetic material, including chromosomes and DNA.
Protein — Important building blocks of the body, composed of amino acids, involved in the formation of body structures and controlling the basic functions of the human body.
Somatic gene therapy — The introduction of genes into tissue or cells to treat a genetic related disease in an individual.
Vectors — Something used to transport genetic information to a cell.



Abella, Harold. "Gene Therapy May Save Limbs." Diagnostic Imaging (May 1, 2003): 16.
Christensen R. "Cutaneous Gene Therapy—An Update." Histochemical Cell Biology (January 2001): 73-82.
"Gene Therapy Important Part of Cancer Research." Cancer Gene Therapy Week (June 30, 2003): 12.
"Initial Sequencing and Analysis of the Human Genome." Nature (February 15, 2001): 860-921.
Kingsman, Alan. "Gene Therapy Moves On." SCRIP World Pharmaceutical News (July 7, 2004): 19:ndash;21.
Nevin, Norman. "What Has Happened to Gene Therapy?" European Journal of Pediatrics (2000): S240-S242.
"New DNA Vaccine Targets Proteins Expressed in Cervical Cancer Cells." Gene Therapy Weekly (September 9, 2004): 14.
"New Research on the Progress of Gene Therapy Presented at Meeting." Obesity, Fitness & Wellness Week (July 3, 2004): 405.
Pekkanen, John. "Genetics: Medicine's Amazing Leap." Readers Digest (September 1991): 23-32.
Silverman, Jennifer, and Steve Perlstein. "Genome Project Completed." Family Practice News (May 15, 2003): 50-51.
"Study Highlights Potential Danger of Gene Therapy." Drug Week (June 20, 2003): 495.
"Study May Help Scientists Develop Safer Mthods for Gene Therapy." AIDS Weekly (June 30, 2003): 32.
Trabis, J. "With Gene Therapy, Ears Grow New Sensory Cells." Science News (June 7, 2003): 355.


National Human Genome Research Institute. The National Institutes of Health. 9000 Rockville Pike, Bethesda, MD 20892. (301) 496-2433.


Online Mendelian Inheritance in Man. Online genetic testing information sponsored by National Center for Biotechnology Information.

gene ther·a·py

alteration of somatic or germ-line DNA to correct or prevent disease; the process of inserting a gene artificially into the genome of an organism to correct a genetic defect or to add a new biologic property or function with therapeutic potential.

In somatic gene therapy, functional DNA sequences are inserted into cells that lack a specific gene or bear a faulty version of it. Vectors include replication-defective viruses, liposomes, and plasmids. For transfer of genetic material by viral infection (called transduction), retroviruses are particularly suitable as vectors because their RNA, converted to DNA by reverse transcriptase, becomes part of the genome of the infected cell. Adenovirus and herpesvirus are also used. Progress has been made in treating several inherited disorders, including severe combined immunodeficiency, cystic fibrosis, and hemophilia B. Gene therapy has several applications in oncology, including the transduction into malignant tumor cells of genes encoding cytokines or coactivation factors to augment host antitumor responses and the transfer of tumor suppressor genes, particularly p53 (the most commonly mutated gene found in human cancers), to enhance the sensitivity of malignant cells to chemotherapeutic agents. Use of viral vectors is associated with a risk of localized and systemic inflammation mediated by cytokines, which can be fatal. Germ-line therapy inserts specific genes directly into the DNA of sperm, egg, or embryo, producing heritable alterations of the genome.

gene therapy

The treatment of certain medical disorders, especially those caused by genetic anomalies or deficiencies, by introducing specific engineered genes into a patient's cells.

gene therapy

a procedure that involves injection of "healthy genes" into the bloodstream of a patient to cure or treat a hereditary disease or similar illness. Blood is withdrawn from the patient; the white cells are separated and cultured in a laboratory. Normal genes from a volunteer are inserted into modified viruses, which, in turn, transfer the normal gene into the chromosomes of the patient's white cells. The white cells containing the normal genes are finally injected into the patient's bloodstream. A clinical application of gene therapy may be found in the treatment of thalassemia, a genetically determined disease, in which efforts have been made to increase hemoglobin F production and improve the level of anemia. Research goals include changing the actual hemoglobin genes in red blood cell precursors or transplantation of normal hemoglobin genes into the bone marrow of thalassemia patients. Also called somatic-cell gene therapy.

gene therapy

Molecular medicine Treatment of disease by replacing, altering or supplementing the genetic structure of either germline–reproductive or somatic–nonreproductive cells a structure that is absent or abnormal and responsible for disease; any of a group of techniques in molecular biology, in which a gene of interest is manipulated, either by mutational inactivation–eg, the 'knock-out mouse', or by replacement, if it causes a particular disease; GT encompasses any therapy that specifically targets the core defect in inherited diseases, either by affecting somatic cells or germ line cells which are usually inserted into the host's genome; strategies for GT include
1. Introduction of a recombinant retrovirus with the missing gene, the promoter, and the gene regulator sequence in the 'package', and.
2. Implantation of the colonies of cells producing the missing factor(s)–eg, α1-antitrypsin deficiency with the missing enzyme introduced into 'carrier' fibroblasts
Gene therapy strategies
Antibody genes Interfere with cancer-related protein activity in tumor cells
Antisense Block synthesis of proteins encoded by a defective gene in the host
Chemoprotection Add proteins to cells that protect them from the toxic effect of chemotherapy
Immunotherapy Enhance host defense against cancer
Oncogene downregulation Turn off genes involved in uncontrolled growth and metastases of tumor cells
Suicide gene/pro-drug therapy Insert proteins that metabolize normal drugs and ↑ their toxicity to proliferating–ie tumor cells
Tumor suppressor genes Replace defective/deficient cancer-inhibiting genes

gene therapy

Germline therapy A format for gene therapy which would prevent passage of parental disease to children by genomic manipulation. See Gene therapy. Cf Eugenics.

gene ther·a·py

(jēn thār'ă-pē)
The process of inserting a gene into an organism to replace or repair gene function to treat a disease or genetic defect.

gene therapy

Medical treatment in which genes are deliberately introduced into general body cells. The method has been in use since 1989. Genes may be delivered directly to target cells by viruses from which viral genes have been removed and replaced by therapeutic genes. In addition, genes may be carried into cells by nutrient substances such as fats proteins or a mineral such as calcium phosphate. Alternatively, some of a person's cells may be removed, genetically modified outside the body, and then reintroduced. The conditions currently most commonly treated by gene therapy are CANCER, AIDS and CYSTIC FIBROSIS. The method is in its early infancy but promises great things. Modification of the human germ line so as to change the heritable state is currently forbidden.

gene therapy

a method for treating DISEASE that involves altering the patient's genetic make-up. Genetic defects may be corrected by replacing the defective GENE(S) or NUCLEOTIDE SEQUENCES, or by supplementing cells with new, functional genes or DNA sequences that will combat the disease. A problem with such therapy is to ensure precise delivery of the genes to the target cells only Unforeseen side effects might occur if the genes enter other cells and become active. Gene therapy is most likely to be successful in treating diseases caused by a single gene mutation, such as SICKLE CELL ANAEMIA and THALASSAEMIA, and has already been attempted in the cure of CYSTIC FIBROSIS. While the normal gene can be expected to replicate as part of cell division during the life of the treated individual, unless the reproductive cells contain the transferred gene the offspring of the individual may carry the defective gene.

performance genes

the potential uses of genetic profiling and gene therapy within sport remain experimental and controversial. Suggested applications include (1) identification of potential athletes by the presence of the so-called performance genes, which may enable an athlete to perform at a higher level by their influence on muscle metabolism and endurance; (2) use as a 'screening' tool to identify athletes with particular body shape, e.g. tall athletes for basketball. This could result in discrimination and have implications for the funding for young athletes, should funding be withheld from those who 'fail' to have the ideal body habitus; (3) identification of those athletes who have a genetic predisposition to sports-related injury. Other moral dilemmas exist in this area. Should the limited funding for genetic research be used to enhance sports performance at the expense of research into disease prevention Should we limit opportunities within sport and exercise because the young person does not have the ideal 'genetic makeup' The World Anti-Doping Agency (WADA) and the International Olympic Committee have recently included the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance in their list of proscribed substances and methods. They will continue to monitor the use of genetic testing and genetic information for identifying or selecting athletes, with a view to developing policies and guidelines for sports organizations and athletes. See also human enhancement technologies (HET).

gene therapy

A therapeutic method in which a defective gene is replaced by a normal copy of itself, thus restoring its function. There are several ways in which a new gene is carried into a diseased cell. A common method uses a retrovirus, an adenovirus or an adeno-associated virus as vectors to introduce genes into cells and DNA. This therapy has been used in the treatment of several eye diseases, especially retinoblastoma and retinitis pigmentosa, but so far with limited success.

gene ther·a·py

(jēn thār'ă-pē)
Inserting a gene into an organism to repair gene function to treat a disease or genetic defect.


the unit of heredity most simply defined as a specific segment of DNA, usually in the order of 1000 nucleotides, that specifies a single polypeptide. Many phenotypic characteristics are determined by a single gene, while others are multigenic. Genes are specifically located in linear order along the single DNA molecule that makes up each chromosome. All eukaryotic cells contain a diploid (2n) set of chromosomes so that two copies of each gene, one derived from each parent, are present in each cell; the two copies often specify a different phenotype, i.e. the polypeptide will have a somewhat different amino acid composition. These alternative forms of gene, both within and between individuals, are called alleles. Genes determine the physical (structural genes), the biochemical (enzymes), physiological and behavioral characteristics of an animal.
The formation of gametes (sperm, ova) involves a process of meiosis, which allows crossing over between four pairs of chromosomes, two derived from each parent, which means that new forms of a particular chromosome are created. Gamete formation also results in cells (gametes) with a haploid (n) set of chromosomes that in fertilization creates a new individual, which is a recombinant of 2n chromosomes, half derived by way of the ovum from the mother and half via the spermatozoa from the father.
Changes in the nucleotide sequence of a gene, either by substitution of a different nucleotide or by deletion or insertion of other nucleotides, constitute mutations which add to the diversity of animal species by creating different alleles and can be used as a basis for genetic selection of different phenotypes. Some mutations, be they a single base change in a single gene or a major deletion, are lethal.

gene action
the way in which genes exert their effects on tissues or processes, e.g. by being dominant or recessive, or partially so, being absent, being sex-linked, being involved in chromosomal aberrations.
allelic g's
different forms of a particular gene usually situated at the same position (locus) in a pair of chromosomes.
gene amplification
see gene duplication (below).
gene bank
the collection of DNA sequences in a given genome. Called also gene library.
barring gene
responsible for the barred pattern on the feathers of Barred Plymouth Rock birds.
gene box
see box (4).
gene clone
see clone.
gene cluster
a group of related genes derived from a common ancestral gene, located closely together on the same chromosome. Called also multigene family.
complementary g's
two independent pairs of nonallelic genes, neither of which is functional without the other.
gene conversion
a non-reciprocal exchange of DNA elements during meiosis which results in a functional rearrangement of chromosomal DNA.
dhfr gene
dihydrofolate reductase gene; an enzyme required to maintain cellular concentrations of H2 folate for nucleotide biosynthesis, and which has been used as a 'selective marker'; cells lacking the enzyme only survive in media containing thymidine, glycine and purines; mutant cells (dhfr) transfected with DNA that is dhfr′ can be selectively grown in medium lacking these elements.
diversity (D) gene
genes located in diversity (D) segment; contribute to the hypervariable region of immunoglobulins.
dominant gene
one that produces an effect (the phenotype) in the organism regardless of the state of the corresponding allele. Examples of traits determined by dominant genes are short hair in cats and black coat color in dogs.
gene duplication
as a result of non-homologous recombination, a chromosome carries two or more copies of a gene.
gene expression
gene frequency
the proportion of the substances or animals in the group which carry a particular gene.
holandric g's
genes located on the Y chromosome and appearing only in male offspring.
immune response (Ir) g's
genes of the major histocompatibility complex (MHC) that govern the immune response to individual immunogens.
jumping gene
see mobile dna.
gene knockout
replacement of a normal gene with a mutant allele, as in gene knockout mice.
lethal gene
one whose presence brings about the death of the organism or permits survival only under certain conditions.
gene library
see gene bank (above).
gene locus
see locus.
mutant gene
one that has undergone a detectable mutation.
non-protein encoding gene
the final products of some genes are RNA molecules rather than proteins.
overlapping g's
when more than one mRNA is transcribed from the same DNA sequence; the mRNAs may be in the same reading frame but of different size or they may be in different reading frames.
gene pool
total of all genes possessed by all members of the population which are capable of reproducing during their lifetime.
gene probe
see probe (2).
recessive gene
one that produces an effect in the organism only when it is transmitted by both parents, i.e. only when the individual is homozygous.
regulator gene, repressor gene
one that synthesizes repressor, a substance which, through interaction with the operator gene, switches off the activity of the structural genes associated with it in the operon.
reporter gene
one that produces products which can be measured and therefore used as an indicator of whether a DNA construct has successfully been transferred.
sex-linked gene
one that is carried on a sex chromosome, especially an X chromosome.
gene splicing
structural gene
nucleotide sequences coding for proteins.
gene therapy
the insertion of functional genes into cells of the host in order to alter its phenotype, usually used to treat an inherited defect.
gene transcription
gene transfer
tumor suppressor g's
a class of genes that encode proteins that normally suppress cell division that when mutated allow cells to continue unrestricted cell division and may result in a tumor.
References in periodicals archive ?
Since their development, gene editing techniques have been used for many purposes: improving bacterial strains used in dairy products, making new animals for research, and experimenting with knocking out disease-inducing mutations in human genes.
The team used new gene editing technology known as the CRISPR/Cas9 system.
Gene editing in food production, regulatory review, and public acceptance.
Gene editing is a recently developed type of genetic engineering in which DNA is inserted, replaced, or removed.
The gene editing, they argue, is also more directed and precise than the existing technique of exposing plants to radiation or chemicals to induce random mutations in hopes of generating a desirable change.
In a July article for eLIFE, a team of researchers led by the Harvard biotechnologist Kevin Esvelt outlines a system that uses the new CRISPR gene editing technique to alter the genomes of wild populations of plants and animals.
One can even imagine using gene editing in combination with stem cells to directly correct certain genetic diseases.
This, when combined with the development of efficient and safe gene editing technologies in human stem cells may greatly help the realization of these expectations," he said.
This gene editing technology may offer potential approaches for the treatment of diseases based upon an error or mutation of a specific gene sequence within a cell, enabling correction of the defect without interfering with cellular function.
Key collaborations using NanoLuc include coupling with 3D cell culture models (InSphero) and combining with genetically-defined reporter cell lines generated using the proprietary GENESIS[TM] gene editing technology (Horizon Discovery Ltd).
The scientists put a new resistance gene into the mosquito's own DNA, using a gene editing method called Crispr.
Key products include SMARTer cDNA synthesis kits for a variety of samples and applications, including NGS; high-performance qPCR and PCR reagents (including the TaKaRa Ex Taq, TaKaRa LA Taq, Titanium, and Advantage enzymes); Cellartis stem cells and stem cell reagents; RT enzymes and SMART library construction kits; the innovative In-Fusion cloning system; Guide-it(TM) gene editing tools; Tet-based inducible gene expression systems; Living Colors fluorescent proteins; and a range of Macherey-Nagel nucleic acid purification tools.