ASPECTS OF GENE THERAPY

QUIAMBAO, JOHN HEART (1-3)

1. What is gene therapy?
Gene therapy is when DNA is introduced into a patient to treat a genetic disease. The new DNA usually
contains a functioning gene to correct the effects of a disease-causing mutation.
• Gene therapy uses sections of DNA? (usually genes?) to treat or prevent disease.
• The DNA is carefully selected to correct the effect of a mutated gene that is causing disease.
• The technique was first developed in 1972 but has, so far, had limited success in treating human
diseases.
• Gene therapy may be a promising treatment option for some genetic diseases.
Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this
technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs
or surgery. Researchers are testing several approaches to gene therapy, including:
 Replacing a mutated gene that causes disease with a healthy copy of the gene.
 Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
 Introducing a new gene into the body to help fight a disease.
Although gene therapy is a promising treatment option for a number of diseases (including inherited
disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under
study to make sure that it will be safe and effective. Gene therapy is currently being tested only for diseases
that have no other cures.

2. How does gene therapy work?

Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or
to make a beneficial protein. If a mutated gene causes a necessary protein to be faulty or missing, gene
therapy may be able to introduce a normal copy of the gene to restore the function of the protein.
A gene that is inserted directly into a cell usually does not function. Instead, a carrier called a vector is
genetically engineered to deliver the gene. Certain viruses are often used as vectors because they can deliver
the new gene by infecting the cell. The viruses are modified so they can't cause disease when used in people.
Some types of virus, such as retroviruses, integrate their genetic material (including the new gene) into a
chromosome in the human cell. Other viruses, such as adenoviruses, introduce their DNA into the nucleus of
the cell, but the DNA is not integrated into a chromosome.
The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body,
where it is taken up by individual cells. Alternately, a sample of the patient's cells can be removed and exposed
to the vector in a laboratory setting. The cells containing the vector are then returned to the patient. If the
treatment is successful, the new gene delivered by the vector will make a functioning protein.
Researchers must overcome many technical challenges before gene therapy will be a practical
approach to treating disease. For example, scientists must find better ways to deliver genes and target them to
particular cells. They must also ensure that new genes are precisely controlled by the body.
NOTES: How is DNA/gene transfer done?
• A section of DNA/gene containing instructions for making a useful protein is packaged within a vector,
usually a virus? bacterium? or plasmid?
• The vector acts as a vehicle to carry the new DNA into the cells of a patient with a genetic disease.
• Once inside the cells of the patient, the DNA/gene is expressed by the cell’s normal machinery leading
to production of the therapeutic protein and treatment of the patient’s disease.

3. Types of gene therapy

 There are two different types of gene therapy depending on which types of cells are treated:
o Somatic gene therapy: transfer of a section of DNA to any cell of the body that doesn’t
produce sperm or eggs. Effects of gene therapy will not be passed onto the patient’s children.
o Germline gene therapy: transfer of a section of DNA to cells that produce eggs or sperm.
Effects of gene therapy will be passed onto the patient’s children and subsequent generations.
SANTIAGO, VINZ (4-5)
4. Is gene therapy safe?
Gene therapy is under study to determine whether it could be used to treat disease. Current research is
evaluating the safety of gene therapy; future studies will test whether it is an effective treatment option. Several
studies have already shown that this approach can have very serious health risks, such as toxicity,
inflammation, and cancer. Because the techniques are relatively new, some of the risks may be unpredictable;
however, medical researchers, institutions, and regulatory agencies are working to ensure that gene therapy
research is as safe as possible.
5. What are the risks, expectations, and outlooks of gene therapy?
Doctors are still experimenting with gene therapy. The long-term safety of such treatments has yet to be
determined. Some gene therapies appear to be effective in curing certain conditions. But there is not enough
evidence about gene therapy as a whole to determine all the possible risks.
Risks
Gene therapy has some potential risks. A gene can't easily be inserted directly into your cells. Rather, it usually
has to be delivered using a carrier, called a vector.
The most common gene therapy vectors are viruses because they can recognize certain cells and carry
genetic material into the cells' genes. Researchers remove the original disease-causing genes from the
viruses, replacing them with the genes needed to stop disease.
This presents the following risks:
 Unwanted immune system reaction. Your body's immune system may see the newly introduced
viruses as intruders and attack them. This may cause inflammation and, in severe cases, organ failure.
 Targeting the wrong cells. Because viruses can affect more than one type of cells, it's possible that
the altered viruses may infect additional cells — not just the targeted cells containing mutated genes. If
this happens, healthy cells may be damaged, causing other illness or diseases, such as cancer.
 Infection caused by the virus. It's possible that once introduced into the body, the viruses may
recover their original ability to cause disease.
 Possibility of causing a tumor. If the new genes get inserted in the wrong spot in your DNA, there is
a chance that the insertion might lead to tumor formation.
Expectations
Currently, the only way for you to receive gene therapy is to participate in a clinical trial. Clinical trials are
research studies that help doctors determine whether a gene therapy approach is safe for people. They also
help doctors understand the effects of gene therapy on the body.
Your specific procedure will depend on the disease you have and the type of gene therapy being used.
For example, in one type of gene therapy:
 You may have blood drawn or you may need bone marrow removed from your hipbone with a large
needle.
 Then, in a lab, cells from the blood or bone marrow are exposed to a virus or another type of vector that
contains the desired genetic material.
 Once the vector has entered the cells in the lab, those cells are injected back into your body into a vein
or into tissue, where your cells take up the vector along with the altered genes.
Viruses aren't the only vectors that can be used to carry altered genes into your body's cells. Other
vectors being studied in clinical trials include:
 Stem cells. Stem cells are the cells from which all other cells in your body are created. For gene
therapy, stem cells can be trained in a lab to become cells that can help fight disease.
 Liposomes. These fatty particles have the ability to carry the new, therapeutic genes to the target cells
and pass the genes into your cells' DNA.
Outlooks
The possibilities of gene therapy hold much promise. Clinical trials of gene therapy in people have shown
some success in treating certain diseases, such as:
 Severe combined immune deficiency
 Hemophilia
 Blindness caused by retinitis pigmentosa
 Leukemia
But several significant barriers stand in the way of gene therapy becoming a reliable form of treatment,
including:
 Finding a reliable way to get genetic material into cells
 Targeting the correct cells
 Reducing the risk of side effects
Gene therapy continues to be a very important and active area of research aimed at developing new, effective
treatments for a variety of diseases.

SAMPANG, PIERRE (6-7)

6. Techniques in Gene Therapy
There are several techniques for carrying out gene therapy. These include:
Gene augmentation therapy
 This is used to treat diseases caused by a mutation that stops a gene from producing a functioning
product, such as a protein?.
 This therapy adds DNA containing a functional version of the lost gene back into the cell.
 The new gene produces a functioning product at sufficient levels to replace the protein that was
originally missing.
 This is only successful if the effects of the disease are reversible or have not resulted in lasting damage
to the body.
 For example, this can be used to treat loss of function disorders such as cystic fibrosis by introducing a
functional copy of the gene to correct the disease (see illustration below).
Gene Inhibition Therapy
 Suitable for the treatment of infectious diseases, cancer and inherited disease caused by inappropriate
gene activity.
 The aim is to introduce a gene whose product either:
o inhibits the expression of another gene
o interferes with the activity of the product of another gene.
 The basis of this therapy is to eliminate the activity of a gene that encourages the growth of disease-
related cells.
 For example, cancer is sometimes the result of the over-activation of an oncogene? (gene which stimulates
cell growth). So, by eliminating the activity of that oncogene through gene inhibition therapy, it is
possible to prevent further cell growth and stop the cancer in its tracks. 
Killing of specific cells

 Suitable for diseases such as cancer that can be treated by destroying certain groups of cells.
 The aim is to insert DNA into a diseased cell that causes that cell to die.
 This can be achieved in one of two ways:
 the inserted DNA contains a “suicide” gene that produces a highly toxic product which kills the diseased
cell
 the inserted DNA causes expression of a protein that marks the cells so that the diseased cells are
attacked by the body’s natural immune system.

It is essential with this method that the inserted DNA is targeted appropriately to avoid the death of cells
that are functioning normally.
 7. Challenges of gene therapy
 Delivering the gene to the right place and switching it on:
o it is crucial that the new gene reaches the right cell

o delivering a gene into the wrong cell would be inefficient and could also cause health problems
for the patient
o even once the right cell has been targeted the gene has to be turned on

o cells sometimes obstruct this process by shutting down genes that are showing unusual activity.

 Avoiding the immune response:

o The role of the immune system is to fight off intruders.

o Sometimes new genes introduced by gene therapy are considered potentially-harmful intruders.

o This can spark an immune response in the patient, that could be harmful to them.

o Scientists therefore have the challenge of finding a way to deliver genes without the immune
system ‘noticing’.
o This is usually by using vectors that are less likely to trigger an immune response.

 Making sure the new gene doesn’t disrupt the function of other genes:
o Ideally, a new gene introduced by gene therapy will integrate itself into the genome of the
patient and continue working for the rest of their lives.
o There is a risk that the new gene will insert itself into the path of another gene, disrupting its
activity. 
o This could have damaging effects, for example, if it interferes with an important gene involved in
regulating cell division, it could result in cancer.
 The cost of gene therapy:
o Many genetic disorders that can be targeted with gene therapy are extremely rare.

o Gene therapy therefore often requires an individual, case-by-case approach. This may be
effective, but may also be very expensive.

POBE, JOHN CARLO (8-9)

8. Types of Diseases for Gene Therapy
There are some FDA-approved gene therapies currently available to patients with diseases such as SMA,
certain blood cancers, and an inherited eye disease. However, most gene therapies are in clinical trials.
Clinical trials are a required research process to understand how a treatment interacts with the body, and if it is
safe and effective before it can be made available to the public.
Gene therapy is aimed at diseases that are rare and often life threatening or debilitating. Rare is defined as
“any disease or disorder affecting fewer than 200,000 people in the U.S.” by the National Institutes of Health.
As of now, there are around 7,000 rare diseases, affecting a total of approximately one in ten people. Many of
these rare diseases are caused by a simple genetic mutation inherited from one or both parents.
 Of gene therapies up for FDA approval over the next five years, 45 percent are anticipated to focus on
cancer treatments (nearly half) and 38 percent (nearly 4 out of 10) are expected to treat rare inherited genetic
disorders.
Some of these inherited diseases include (but are not limited to):
Hematology

 Hematology is the study of blood and blood disorders. Hematologists and hematopathologists
are highly trained healthcare providers who specialize in diseases of the blood and blood
components. blood and bone marrow cells.

Hematological Disorders
 Anemia.
 Aplastic Anemia.
 Hemolytic Anemia.
 Iron Deficiency Anemia.
 Megaloblastic (Pernicious) Anemia.
 Sickle Cell Disease.
 Thalassemia. Alpha Thalassemia. Beta Thalassemia (Cooley's Anemia)
Neurology

 Neurology is the branch of medicine concerned with the study and treatment of disorders of the
nervous system. The nervous system is a complex, sophisticated system that regulates and
coordinates body activities. It has two major divisions: Central nervous system: the brain and spinal
cord.

Neurological Disorders
 Acute Spinal Cord Injury
 Alzheimer's Disease
 Amyotrophic Lateral Sclerosis (ALS)
 Ataxia
 Bell's Palsy
 Brain Tumors
 Cerebral Aneurysm
 Epilepsy and Seizures
Musculoskeletal

 Your musculoskeletal system includes bones, muscles, tendons, ligaments and soft tissues. They
work together to support your body's weight and help you move. Injuries, disease and aging can
cause pain, stiffness and other problems with movement and function.

Musculoskeletal Disorders
 Carpal Tunnel Syndrome
 Tendonitis
Retinology

 A retina specialist is a medical doctor who has specialized in ophthalmology and sub-specialized in
diseases and surgery of the vitreous body of the eye and the retina. This subspecialty is sometimes
known as vitreoretinal medicine. Retina specialists are highly trained.

Retinal Disorders
  Retinal tear
 Retinal detachment
 Diabetic retinopathy
 Epiretinal membrane
 Macular hole
 Macular degeneration
 Retinitis pigmentosa
Oncology

 Oncology is the study of cancer. An oncologist is a doctor who treats cancer and provides medical
care for a person diagnosed with cancer.

Oncological Disorders
 Osteoid Osteoma.
 Non Hodgkin Lymphoma.
 Testicular Cancer.
 Multiple Myeloma.
 Breast Cancer.

9. When should I ask my doctor about gene therapy?

Researchers are investigating gene therapy to treat cancer, eye diseases, some genetic conditions and
HIV/AIDS. If you are interested in participating in a clinical trial involving gene therapy, speak with your doctor.
Your doctor can help determine whether gene therapy might treat your condition.