Gene Therapy
Presentation By:
Michelle Hollenbeck
Angie Cirello
Overview of Gene Therapy
Gene therapy is the process
of inserting new genes into a
person with a defective gene
to help correct the problem
the mutation in the gene is
causing.
The effect of a mutated gene
can show up as cancer,
blindness, and many other
types of diseases.
Genes are found in DNA
located in the nucleus of each
cell and they make up
characteristics unique to each
individual.
Genes with in a chromosome
History of Gene Therapy
1964 Nobel Prize winners Ed
Tatus, Joshua Lederberg, and
Arthur Kornberg first suggested
that diseases could possibly be
treated by replacing defective
genes with functioning genes.
In the 1980s genes were first
being sequenced and cloned
which eventually led to introducing
genes into human cells with the
goal of curing disease Arthur Kornberg
Gene therapy clinical trials began
in Europe in the 1990s and today
there are over 500 trials with
5,000 patients
Two Types of Gene Therapy
Somatic:
This type of therapy is most
common and involves changing
the genes in a developed human
with a genetic disease. This
gene will not be passed on to
future generations.
Germline:
This type of therapy involves
altering genes in sex cells to stop
genetic mutations from being
passed on to future offspring.
This type of therapy is not
receiving much attention because
it is more controversial.
How Does Gene Therapy Work?
A carrier molecule called a vector, usually a virus, is
injected with a strand of healthy DNA after the viruses
DNA has been removed.
This vector is sent to a target cell in a patient with a
defective gene where it enters the nucleus and the
genes in the new DNA are activated.
Then, these genes are either integrated into the cells
DNA, hopefully fixing the defect in the gene. Or
sometimes, genes are only temporarily located in the
cell and are discarded after a certain amount of time.
This depends on the type of vector used.
Click here for an animation.
Vectors
Viral
DNA is inserted into a virus which is then sent to a target
cell
Retrovirus
Adenovirus
Adeno-Associated Virus
Herpes Simplex Virus
Non-Viral
Often DNA in a circular strand called a plasmid is sent in
to a target cell
Liposome
Naked DNA
More on Vectors
Viruses by nature are designed to target cells and transfer
their genetic information into another cell. This makes
them the perfect candidate for gene therapy.
They are able to be modified so they target specific cells
and become less harmful to your body.
However, they are only able to hold a certain amount of
DNA, which isn’t always enough, and they can sometimes
cause harmful immune responses.
Non-viral vectors are generally plasmids and are more
commonly used in ex vivo gene therapy. They rarely have
immune responses but can sometimes be toxic.
They rarely integrate their genetic material into the cells,
so they are only temporary fixes for a genetic problem.
Retroviruses In Depth
RNA containing retroviruses infect a cell by injecting
RNA and enzymes into the cell
Then a process called reverse transcription occurs
which means making a DNA molecule from a strand of
RNA.
The virus contains an enzyme called reverse
transcriptase which initiates this process. Another
enzyme called integrase then causes the DNA to be
incorporated into the host cell’s chromosomes.
When the host cell divides the new copies will have the
new gene
Delivery Methods: Ex Vivo
Ex Vivo
First type of gene therapy performed
Cells are removed from a patient and combined with vectors
outside of the body.
They are then modified with new genes and put back into the
patients body where they will hopefully reproduce and create
healthy DNA for the patient.
Treatment is best when tissue can be easily removed and replaced
Delivery Methods: In Vivo
In Vivo
A vector with healthy DNA in inserted directly into the
body where it will hopefully reach a cells nucleus and
integrate into the DNA.
This approach is riskier because the DNA must
escape an immune response in order to work.
What Makes a Disease a Good
Candidate For Gene Therapy?
If the condition is a result of a genetic mutation
If you know which genes are involved in the condition
The best candidates involve only a single gene mutation
Knowledge of the disease
Which tissues are affected
Role of proteins created by that gene and the effect of
the mutation of the proteins
How easy it is to reach the effected tissue
If adding a healthy gene would fix the problem created
by the defective gene
What Diseases Does Gene
Therapy Treat?
Genetic Diseases
Hemophilia
Cystic Fibrosis Cystic Fibrosis
Immune Disorders
Metabolic Disorders
X-SCID
Acquired Diseases
Cancer
AIDS
Diabetes Cancer Tumor
Heart Disease
Cardiovascular Disease
In a cardiovascular
condition called Ischemia
patients have blood flow
restricted in a part of the
body
Gene therapy has been
used to restore circulation
for Ischemia patients
This process has also
helped amputee patients
save a limb
Gene therapy has also
been effective in keeping
formerly blocked arteries
clear
SCID
Sever Combined Immunodeficiency
Genetically acquired
Extremely susceptible to disease and forced to live in sterile
conditions
Gene therapy has been used to treat these patients
A leukemia virus is used to deliver the functioning gene that in SCID
patients is defective
Some children cured -- but some children little or no recovery/death
from gene therapy complications
Current Research
At this point some number of patients have
been treated by gene therapy
Although most have been successful there
are many complications that go along with
gene therapy
All trials have been in the research stage
Recently scientists have discovered that
turning off genes may be a cure to
Huntington’s disease
Able to cure sickle cell anemia in mice -
maybe soon in humans A retinal photograph of a
Briard dog with the
Dogs with inherited eye disease treated and inherited eye disease
vision was completely restored through gene
therapy - humans born blind may one day
see
Complications
Complications are caused when a gene doesn’t attach into the genome in
the right spot
Genes may be attacked by a patients immune system when entering the
body causing the trial to be ineffective
In one case a patient suffering from ornithine transcarboxylase deficiency
died from organ failure four days after gene therapy treatment. This failure
was likely an immune response to his adenovirus carrier
Patients may develop cancer or suffer other side effects
Some disorders involve multiple genes (heart disease, high blood pressure,
Alzheimer's disease, and arthritis--really common)
Laws restricting gene therapy have been common since 1990s
Limited knowledge
Genes unknown for certain diseases
Cost--gene therapy is very expensive
Benefits to Gene Therapy
Rather than treating the
symptoms of a disease it treats
the root of the problem, DNA
Diseases such as cancer and
AIDS that currently have no cure
have great potential to possibly
be treated in the near future by
gene therapy
Cures disease for life, and
possibly protect children from
same disease
Possible to treat disease of
unborn baby
Questions to Consider
When should gene therapy be used? Should it be used to treat critically ill
patients? Should it be used to treat babies and children?
What effect would gene therapy have on future generations if germline
(reproductive) cells were genetically altered? How might this alteration
affect human variation?
Who should decide what are "good" or "bad" uses of genetic
modifications? How do you define "normal" with regard to human beings?
What if we could alter human traits not associated with disease?
Would it be okay to use gene therapy to improve or enhance a person's
genetic profile?
Who will have access to gene therapy, treatments and long-term
follow-ups? Will gene therapy and genetic enhancements create an
advantage for those who can afford it?
Source: http://gslc.genetics.utah.edu/units/genetherapy/gtissues/
Bibliography
Gene Therapy. Retrieved February 11th, 2005 from http://www.ornl.gov.
Gene Therapy Questions & Answers. Retrieved February 11th, 2005 from http://www.cancer.org
Gene Therapy Caused T Cell Leukemia. Retrieved February 11th 2005 from
http://www.biomedicalcentral.com
Gene Therapy. Retrieved February 11th 2005 from http://www.americanheart.org
Bubble Boy Saved By Gene Therapy. Retrieved February 11th, 2005 from
http://news.bbc.co.uk/1/hi/health/1906999.stm
Gene Therapy. Retrieved February 11th 2005 from http://en.wikipedia.org/wiki/Gene_Therapy
Choosing Targets for Gene Therapy. Retrieved from
http://gslc.genetics.utah.edu/units/genetherapy/gttargets/
Gene Therapy. Retrieved February 11th 2005 from http://www.accessexcellence.org