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| Gene therapy attempts to treat genetic diseases
at the molecular level by correcting what is wrong with defective
genes.
Clinical research into gene therapy’s safety and effectiveness
has just begun. No one knows if gene therapy will work, or for what
diseases. If gene therapy is successful, it could work by preventing
a protein from doing something that causes harm, restoring the normal
function of a protein, giving proteins new functions, or enhancing
the existing functions of proteins.
How Do You
Do It? Gene therapy
relies on finding a dependable delivery system to carry the correct
gene
to the affected cells.
The gene must be delivered inside the target cells and work properly
without causing adverse effects. Delivering genes that will work correctly
for the long term is the greatest challenge of gene therapy. |
This photograph is of an adenovirus. Viruses are
often used by researchers to deliver the correct gene to cells. Viruses
deposit their own genetic material into host cells to instruct those
cells to make more viruses. In gene therapy, the DNA for the desired
gene is inserted into the genetic material of the virus. The
virus is engineered so that it cannot reproduce, but it
does deliver its new genetic material which contains the desired DNA.
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| Adenovirus.
Courtesy of Child Health and Human Development |
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Gene therapy researchers are
investigating ways other than viruses to deliver the correct gene
to cells. Fatty molecules
known as liposomes
may also be used as can micropipettes,
sometimes called "gene guns" to insert genes into cells
physically.
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| Liposome.
Courtesy of Liposome Technology, Inc. |
| ADA: The
First Gene Therapy Trial |
A four-year old girl became the first gene therapy patient on September
14, 1990 at the NIH Clinical Center. She has adenosine deaminase (ADA)
deficiency, a genetic disease which leaves her defenseless against
infections. White
blood cells were taken from her, and the normal genes for making
adenosine deaminase were inserted into them. The corrected cells were
reinjected into her. Dr. W. French Anderson helped develop this landmark
clinical trial when he worked at the National Heart, Lung, and Blood
Institute. |
Human ex vivo Gene Therapy
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| Below
is a Timeline Telling the Story of Developing the First Human Gene
Therapy: |
1985
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Culver,
Anderson, and Blaese with gene therapy patients.
Courtesy of Dr. Kenneth Culver, Novarti Pharmaceuticals Corporation |
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The laboratories of Drs. W. French
Anderson and Michael Blaese in the National Heart, Lung, and Blood
Institute and the National Cancer Institute worked together to show
that cells
from patients with ADA deficiency can be corrected in tissue
culture. They used a retrovirus
to carry the correct human ADA gene to the cells. Here, Drs. Kenneth
Culver (then of the NHLBI), W. French Anderson, and Michael Blaese
pose with gene therapy patients. |
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1986
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The team studied how
safely and efficiently the correct genes were transfered into bone
marrow cells in animals. The process wasn’t harmful, but the
number of cells that received the correct gene was too small to be
a useful treatment. |
1988
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White
Blood Cell.
Courtesy of Dr. Kenneth Culver, Novarti Pharmaceuticals Corporation. |
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The researchers decided to use white
blood cells (T cells), pictured here in tissue culture, instead of
bone marrow cells. This switch greatly increased the number of correct
genes taken up by the cells in the animal experiments -- the experiments
were so successful that the team began to look for ways to test the
delivery system in people. |
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1989
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The team worked with
Dr. Steven Rosenberg to test the safety and effectiveness of the gene
therapy process in cancer patients. The team grew tumor
infiltrating lymphocytes (TIL cells) from people with the deadly
cancer malignant melanoma,
and then they engineered a virus to put a DNA
marker into those cells. These "marked TIL cells" helped
the researchers learn two things: which TIL cells work best for cancer
treatment; and that the engineered virus can be used safely in humans. |
1990
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Drawing
of infusion procedure by patient. Courtesy
of the National Museum of American History |
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Drs. Anderson, Blaese,
and Kenneth Culver used a virus to deliver the correct ADA gene to
a four-year old girl and a nine-year old girl with ADA deficiency.
Each girl was given repeated treatments over a period of two years.
The nine-year old girl drew several pictures of her treatment -- here
she is receiving an infusion of her own corrected cells. |
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1993
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Researchers used gene
therapy to treat newborn babies with ADA deficiency. The normal ADA
genes were delivered to immature blood cells isolated from the babies’
umbilical cords. It is hoped these special cells will provide longer-lasting
benefits. |
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Present
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The two original ADA patients attend
school and are leading normal lives. The newborn patients have shown
steady increases in ADA in their immune cells following a single gene
therapy treatment. But although the promise of gene therapy is great,
many scientific obstacles remain before it becomes a practical form
of therapy. |
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