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, andstress. 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), Duchennemuscular 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 humanimmunodeficiency 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.
Resources
Periodicals
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.
Organizations
National Human Genome Research Institute. The National Institutes of
Health. 9000 Rockville Pike, Bethesda, MD 20892. (301) 496-2433. http://www.nhgri.nih.gov.
Other
Online Mendelian Inheritance in Man. Online genetic
testing information sponsored by National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/Omim/.
Gale Encyclopedia of Medicine. Copyright 2008 The Gale Group, Inc. All
rights reserved.
ablation therapy the destruction of small areas of
myocardial tissue, usually by application of electrical or chemical energy, in
the treatment of some tachyarrhythmias.
adjuvant therapy the use of chemotherapy or radiotherapy in addition to surgical resection in the treatment of cancer.
antiplatelet therapy the use of platelet-modifying agents
to inhibit platelet adhesion or aggregation and so prevent thrombosis, alter
the course of atherosclerosis, or prolong vascular graft patency.
art therapy the use of art, the creative
process, and patient response to the products created for the treatment of
psychiatric and psychologic conditions and for rehabilitation.
aversion therapy , aversive therapy that
using aversive conditioning to reduce or eliminate undesirable behavior or
symptoms; sometimes used synonymously with aversive conditioning.
behavior therapy a therapeutic approach that focuses
on modifying the patient's observable behavior, rather than on the conflicts
and unconscious processes presumed to underlie the behavior.
biological therapy treatment of disease by injection of
substances that produce a biological reaction in the organism.
chelation therapy the use of a chelating agent to remove toxic metals
from the body, used in the treatment of heavy metal poisoning. In complementary medicine, also used for the
treatment ofatherosclerosis and other disorders.
cognitive therapy , cognitive-behavioral
therapy that based on the theory that emotional problems result from
distorted attitudes and ways of thinking that can be corrected, the therapist
guiding the patient to do so.
convulsive therapy treatment of mental disorders,
primarily depression, by induction of convulsions; now it is virtually always
by electric shock (electroconvulsive t.) .
couples therapy marital t.
dance therapy the therapeutic use of movement to
further the emotional, social, cognitive, and physical integration of the
individual in the treatment of a variety of social, emotional, cognitive, and
physical disorders.
electroconvulsive therapy (ECT) a treatment for mental
disorders, primarily depression, in which convulsions and loss of consciousness
are induced by application of brief pulses of low-voltage alternating current
to the brain via scalp electrodes.
electroshock therapy (EST) electroconvulsive t.
endocrine therapy treatment of disease by the use of
hormones.
estrogen replacement therapy
administration of an estrogen to treat estrogen deficiency, as
that following menopause; in women with a uterus, a progestational agent is usually included
to prevent endometrial hyperplasia.
enzyme therapy in complementary medicine, the oral
administration of proteolytic enzymes to improve immune
system function; used for a wide variety of disorders and as adjunctive therapy
in cancer treatment.
family therapy group therapy of the members of a
family, exploring and improving family relationships and processes and thus the
mental health of the collective unit and of individual members.
fibrinolytic therapy the use of fibrinolytic agents
(e.g., prourokinase) to lyse thrombi in patients with acute peripheral arterial
occlusion, deep venous thrombosis, pulmonary embolism, or acute myocardial
infarction.
gene therapy manipulation of the genome of an
individual to prevent, mask, or lessen the effects of a genetic disorder.
group therapy psychotherapy carried out regularly
with a group of patients under the guidance of a group leader, usually a
therapist.
highly active antiretroviral therapy (HAART) the
aggressive use of extremely potent antiretroviralagents in the treatment of human immunodeficiency virus infection.
hormonal therapy , hormone therapy endocrine t.
hormone replacement therapy the
administration of hormones to correct a deficiency, such as postmenopausal estrogen replacement ttherapy.
immunosuppressive therapy treatment with agents, such
as x-rays, corticosteroids, or cytotoxic chemicals, that suppress the immune response to antigen(s); used in
conditions such as organ transplantation, autoimmune disease, allergy, multiple
myeloma, and chronic nephritis.
inhalation therapy former name for respiratory care (2).
light therapy
1. phototherapy (def. 1).
2. photodynamic t.
marital therapy a type of family therapy aimed at
understanding and treating one or both members of a couple in the context of a
distressed relationship, but not necessarily addressing the discordant
relationship itself; sometimes used more restrictively as a synonym of marriage therapy .
marriage therapy a subset of marital therapy (q.v.) that focuses
specifically on the bond of marriage between two people, enhancing and
preserving it.
massage therapy the manipulation of the soft tissues
of the body for the purpose of normalizing them, thereby enhancing health and
healing.
milieu therapy treatment, usually in a psychiatric
hospital, that emphasizes the provision of an environment and activities
appropriate to the patient's emotional and interpersonal needs.
music therapy the use of music to effect positive
changes in the psychological, physical, cognitive, or social functioning of
individuals with health or educational problems.
occupational therapy the therapeutic use of self-care,
work, and play activities to increase function, enhance development, and
prevent disabilities.
oral rehydration therapy (ORT) oral administration of
a solution of electrolytes and carbohydrates in the treatment of dehydration.
orthomolecular therapy treatment of disease based on
the theory that restoration of optimal concentrations of substances normally
present in the body, such as vitamins, trace elements, and amino acids, will
effect a cure.
photodynamic therapy intravenous administration of
hematoporphyrin derivative, which concentrates selectively in metabolically
active tumor tissue, followed by exposure of the tumor tissue to red laser
light to produce cytotoxic free radicals that destroy
hematoporphyrin-containing tissue.
physical therapy
1. treatment by physical means.
2. the health profession concerned with the promotion of
health, the prevention of disability, and the evaluation and rehabilitation of
patients disabled by pain, disease, or injury, and with treatment by physical
therapeutic measures as opposed to medical, surgical, or radiologic measures.
poetry therapy a form of bibliotherapy in which a selected poem,
which may be created by the patient, is used to evoke feelings and responses
for discussion in a therapeutic setting.
PUVA therapy a form of photochemotherapy for skin
disorders such as psoriasis and vitiligo; oral psoralen administration is
followed two hours later by exposure to ultraviolet light.
radiation therapy radiotherapy.
relaxation therapy any of a number of techniques for
inducing the relaxation response, used for the reduction of
stress; useful in the management of a wide variety of chronic illnesses caused
or exacerbated by stress.
replacement therapy
1. treatment to replace deficiencies in body products by
administration of natural or synthetic substitutes.
2. treatment that replaces or compensates for a
nonfunctioning organ, e.g., hemodialysis.
respiratory therapy see under care.
substitution therapy the administration of a hormone to
compensate for glandular deficiency.
thrombolytic therapy fibrinolytic t.
thyroid replacement therapy treatment
with a preparation of a thyroid hormone.
Dorland's Medical Dictionary for Health Consumers. © 2007 by Saunders,
an imprint of Elsevier, Inc. All rights reserved.
|
gene therapy
n.
A technique for the treatment of genetic disease in which a gene that
is absent or defective is replaced by a healthy gene.
|
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.
Mosby's Medical Dictionary, 8th edition. © 2009, Elsevier.
gene,
n See family practice.
(ho´meoboks”),
n a gene containing a DNA sequence called the homeobox, which is very similar between species and encodes a DNA-binding domain in the resulting protein molecule. Homeobox genes usually play a role in controlling development of the organism.
n a gene containing a DNA sequence called the homeobox, which is very similar between species and encodes a DNA-binding domain in the resulting protein molecule. Homeobox genes usually play a role in controlling development of the organism.
gene locus,
n See locus, gene.
gene, sex-linked,
n a gene located in a sex chromosome.
gene therapy,
n a procedure that involves injection of “health genes”
into the bloodstream of a patient to cure or treat a hereditary disease or
similar illness.
Mosby's Dental Dictionary, 2nd edition. © 2008 Elsevier, Inc. All rights
reserved.
gene
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
see expression (3).
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
see 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
see transcription.
gene transfer
see recombination.
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.
Saunders Comprehensive Veterinary Dictionary, 3 ed. © 2007 Elsevier,
Inc. All rights reserved
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.
Millodot: Dictionary of Optometry and Visual Science, 7th edition. ©
2009 Butterworth-Heinemann
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.
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The
McGraw-Hill Companies, Inc.
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.
Farlex Partner Medical Dictionary © Farlex 2012
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.
Medical Dictionary for the Health Professions and Nursing © Farlex 2012
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.
Medical Dictionary for the Dental Professions © Farlex 2012
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).
SOURCE
http://medical-dictionary.thefreedictionary.com/Gene+Therapy
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