This is a SIM that others can use for teaching all bout gene therapy :))

1. Strategic Intervention
Material
Gene
Therapy
Aubrey Arenas
Mikah De Vera
Jairra Mae Madrigalejo
Jhon Neil Barrun
Yllian San Luis

2. Introduction
:
Good day students and teachers! We are assigned to make our
Strategic Intervention Material or simply called SIM all about Gene Therapy.
What is Gene Therapy? It is a technique for correcting defective
genes that are responsible for disease development. There are four
approaches in gene therapy; a normal gene inserted to compensate for a
nonfunctional gene; an abnormal gene traded for a normal gene; an
abnormal gene repaired through selective reverse mutation; it change the
regulation of gene pairs.
And as we go on to our lesson, we will learn different things
that will enhance our knowledge and will help us encourage
many
people to cure certain diseases like hemophilia,
leukemia, etc. And
also we want to teach them the studies
that we’ve made and to help
them understand more easily
from our easy module.
- Miracle Therapy

3. 4 pics, 1 word
Directions: Use the following pictures to identify the terms about gene therapy.
A
S
P
G
E
R
E
T
O
R
H
N
E
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K
P
A
I
 The basic unit of heredity
 Proteins carry out most of life’s function.
 When altered causes dysfunction of a protein
A
S
V
L
E
R
C
T
O
R
L
N
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K
V
A
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 It is the basic structural, functional and biological
unit of all known living organism.
 The smallest unit of life that is classified as a
living thing, and are often called the "building
blocks of life".

4. 4 pics, 1 word
G
I
N
G
E
N
C.
T
E
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R
N
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 Also called genetic modification, is the direct
manipulation of an organism's genome using biotech.
A
S
V
L
E
R
U
K
O
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M
E
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 A malignant progressive disease in which the bone
marrow and other blood-forming organs produce
increased numbers of immature or abnormal
leucocytes. These suppress the production of normal
blood cells, leading to anemia and other symptoms.

5. 4 pics, 1 word
O
T
C
V
L
A
C.
R
V
E
R
N
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G
.I
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 A tool commonly used by molecular biologists to
deliver genetic material into cells. This process can
be performed inside a living organism or in cell culture
R
S
S
T
E
R
U
K
O
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L
M
E
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K
V
A
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 Created double stranded DNA copies from RNA
genome

6. 4 pics, 1 word
O
T
C
V
D
A
C.
R
V
E
R
N
E
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U
.I
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 Are double stranded DNA genome that cause
respiratory, intestinal, and eye infections in humans
 The inserted DNA is not incorporate into genome
R
S
S
T
E
R
U
K
O
R
L
R
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R
V
A
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 A person who has a recessive mutated gene, together
with its normal allele. Carriers do not usually develop
disease but can pass the mutated gene on to their
children.

7. 4 pics, 1 word
O
T
C
V
L
A
C.
R
M
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 A protein that facilitates a specific chemical reaction.
R
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U
K
O
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L
N
E
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K
V
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 A group of identical genes, cells, or organisms derived
from a single ancestor.

8. Pre-Test
1. When was gene therapy first captulized?
a.1972
b.1987
c. 1990
d. 1980
a. Processing gene therapy
b. Autosomal gene therapy
c. Preventive gene therapy
d. Multiple gene therapy
2. It is the repair of a gene with a mutation associated with a progressive disease, prior to the
expression of a medical condition, to prevent that expression?
3. It is a type of gene therapy where the therapeutic genes are transferred into the somatic cells (non
sex-cells), or body, of a patient?
a. Germ line gene therapy c. Autosomal gene therapy
b. Preventive gene therapy
d. Somatic gene therapy
4. These are the diseases that can cure by gene therapy except one.
a. Parkinson's disease
b. Diabetes
c. Multiple myeloma
d. Leber's congenital amaurosis
5. Who first approved gene therapy?
a. FDA
b. ADA-SCID
d. DFA
c. WHO

9. Pre-Test
6. When was the first gene therapy performed?
a. September 14, 1902
b. September 14,1990
c. September 14, 1995
d. September 14, 1972
7. Who was the first person that was treated by gene therapy?
a. Jesse Gelsinger
b. Ashenti DeSilva
c. Ashanti DeSilva
d. Jesse Gilsinger
8. These are the problems encountered in gene therapy except one.
a. Short life span
b. Viral Vectors
c. Multigene Disorders
d. Fever
9. It replaces a faulty gene or adds a new gene in an attempt to cure disease or improve your
body's ability to fight disease?
a. Miracles
b. Gene therapy
10. What do you mean by SCID?
a. Severe Combined Immunodeficiency
b.Surgical Combined Immunodeficiency
c. Herbal
d. Medicines
c. Severe Common Immunodeficiency
d. Stone Cloning Immunodeficiency

10. Miracle Therapy:
Gene

Are carried on a chromosome

The basic unit of heredity

Encode how to make a protein
 DNARNA proteins

Proteins carry out most of life’s function.

When altered causes dysfunction of a protein

When there is a mutation in the gene, then it will change the codon, which will change
which amino acid is called for which will change the conformation of the protein which will
change the function of the protein. Genetic disorders result from mutations in the genome.
What is Gene Therapy?
It is a technique for correcting defective genes that are responsible for disease development
There are four approaches:
1.
A normal gene inserted to compensate for a nonfunctional gene.
2.
An abnormal gene traded for a normal gene
3.
An abnormal gene repaired through selective reverse mutation
4.
Change the regulation of gene pairs

11. Gene Therapy
The Beginning…
In the 1980s, Scientists began to look into gene therapy.
 They would insert human genes into a bacteria cell.
 Then the bacteria cell would transcribe and translate the information into a protein
 Then they would introduce the protein into human cells
The First Case
The first gene therapy was performed on September 14 th, 1990
 Ashanti DeSilva was treated for SCID

Severe combined immunodeficiency
 Doctors removed her white blood cells, inserted the missing gene into the WBC, and
then put them back into her blood stream.
 This strengthened her immune system
 Only worked for a few months 
How it works?
A vector delivers the therapeutic gene into a patient’s target cell
The target cells become infected with the viral vector
The vector’s genetic material is inserted into the target cell
Functional proteins are created from the therapeutic gene causing the cell to return to a
normal state

12. Gene Therapy
Viruses
Replicate by inserting their DNA into a host cell
Gene therapy can use this to insert genes that encode for a desired protein to create the
desired trait
Four different types
Retroviruses
Created double stranded DNA copies from RNA genome

The retrovirus goes through reverse transcription using reverse transcriptase and RNA

the double stranded viral genome integrates into the human genome using integrase

integrase inserts the gene anywhere because it has no specific site

May cause insertional mutagenesis

One gene disrupts another gene’s code (disrupted cell division causes
cancer from uncontrolled cell division)

vectors used are derived from the human immunodeficiency virus (HIV) and are being
evaluated for safety
Adenoviruses
Are double stranded DNA genome that cause respiratory, intestinal, and eye infections
in humans
The inserted DNA is not incorporate into genome
Not replicated though 

Has to be reinserted when more cells divide
Ex. Common cold

13. Gene Therapy
Adeno-associated Viruses
Adeno-associated Virus- small, single stranded DNA that insert genetic material at a specific point on
chromosome 19
From parvovirus family- causes no known disease and doesn't trigger patient immune response.
Low information capacity
gene is always "on" so the protein is always being expressed, possibly even in instances when it isn't needed.
hemophilia treatments, for example, a gene-carrying vector could be injected into a muscle, prompting the
muscle cells to produce Factor IX and thus prevent bleeding.

Study by Wilson and Kathy High (University of Pennsylvania), patients have
not
needed Factor IX injections for more than a year
Herpes Simplex Viruses
Double stranded DNA viruses that infect neurons
Non-viral Options
Direct introduction of therapeutic DNA

But only with certain tissue

Requires a lot of DNA
Creation of artificial lipid sphere with aqueous core, liposome

Carries therapeutic DNA through membrane
Chemically linking DNA to molecule that will bind to special cell receptors

DNA is engulfed by cell membrane

Less effective 
Trying to introduce a 47th chromosome

Exist alongside the 46 others

Could carry a lot of information

But how to get the big molecule through membranes?

14. Gene Therapy
Current Status
FDA hasn’t approved any human gene therapy product for sale
Reasons:
In 1999, 18-year-old Jesse Gelsinger died from multiple organ failure 4 days after treatment for omithine
transcarboxylase deficiency.

Death was triggered by severe immune response to adenovirus carrier
January 2003, halt to using retrovirus vectors in blood stem cells because children developed leukemia-like
condition after successful treatment for X-linked severe combined immunodeficiency disease
Problems with Gene Therapy
Short Lived

Hard to rapidly integrate therapeutic DNA into genome and rapidly dividing nature of cells prevent
gene therapy from long time

Would have to have multiple rounds of therapy
 Immune Response

new things introduced leads to immune response

increased response when a repeat offender enters
Viral Vectors

patient could have toxic, immune, inflammatory response

also may cause disease once inside
Multigene Disorders

Heart disease, high blood pressure, Alzheimer’s, arthritis and diabetes are
hard to treat because you need to introduce more than one gene
May induce a tumor if integrated in a tumor suppressor gene because
insertional
mutagenesis

15. Gene Therapy
Unsuccessful Gene therapies
Jesse Gelsinger, a gene therapy patient who lacked ornithine transcarbamylase activity, died in 1999.
Within hours after doctors shot the normal OTC gene attached to a therapeutic virus into his liver, Jesse
developed a high fever. His immune system began raging out of control, his blood began clotting, ammonia
levels climbed, his liver hemorrhaged and a flood of white blood cells shut down his lungs.
One problem with gene therapy is that one does not have control over where the gene will be inserted into the
genome. The location of a gene in the genome is of importance for the degree of expression of the gene and for
the regulation of the gene (the so-called "position effect"), and thus the gene regulatory aspects are always
uncertain after gene therapy
Successful Gene Therapy for Severe Combine Immunodeficiency
Infants with severe combined immunodeficiency are unable to mount an adaptive immune response, because
they have a profound deficiency of lymphocytes.
severe combined immunodeficiency is inherited as an X-linked recessive disease, which for all practical
purposes affects only boys. In the other half of the patients with severe combined immunodeficiency, the
inheritance is autosomal recessive — and there are several abnormalities in the immune system when the
defective gene is encoded on an autosome.
Severe Combine Immunodeficiency Continued
A previous attempt at gene therapy for immunodeficiency was successful in children with severe combined
immunodeficiency due to a deficiency of adenosine deaminase. In these patients,
peripheral T cells
were transduced with a vector bearing the gene for adenosine
deaminase. The experiment was extremely
labor intensive, because mature
peripheral-blood T cells were modified rather than stem
cells, and the procedure therefore had to be repeated many times to achieve success.

16. Gene Therapy
Successful One Year Gene Therapy Trial For Parkinson's Disease
Neurologix a biotech company announced that they have successfully completed its landmark Phase I trial of
gene therapy for Parkinson's Disease.
This was a 12 patient study with four patients in each of three dose escalating cohorts. All procedures were
performed under local anesthesia and all 12 patients were discharged from the hospital within 48 hours of the
procedure, and followed for 12 months. Primary outcomes of the study design, safety and tolerability, were
successfully met. There were no adverse events reported relating to the treatment.
Parkinson's Disease Cont.
The gene transfer procedure utilized the AAV (adeno-associated virus) vector, a virus that has been used
safely in a variety of clinical gene therapy trials, and the vehicle that will be used in all of the company's first
generation products, including epilepsy and Huntington's disease. In its Parkinson's disease trial, Neurologix
used its gene transfer technology.
Recent Developments
Genes get into brain using liposomes coated in polymer call polyethylene glycol

potential for treating Parkinson’s disease
RNA interference or gene silencing to treat Huntington’s

siRNAs used to degrade RNA of particular sequence

abnormal protein wont be produced
Create tiny liposomes that can carry therapeutic DNA through
pores of nuclear membrane
 Sickle cell successfully treated in mice

17. http://www.wellesley.edu/Biology/Courses/219/Gen_news/i3_Gene_Therapy.jpg

18. Post-Test
1. When was gene therapy first captulized?
a.1972
b.1987
c. 1990
d. 1980
a. Processing gene therapy
b. Autosomal gene therapy
c. Preventive gene therapy
d. Multiple gene therapy
2. It is the repair of a gene with a mutation associated with a progressive disease, prior to the
expression of a medical condition, to prevent that expression?
3. It is a type of gene therapy where the therapeutic genes are transferred into the somatic cells (non
sex-cells), or body, of a patient?
a. Germ line gene therapy c. Autosomal gene therapy
b. Preventive gene therapy
d. Somatic gene therapy
4. These are the diseases that can cure by gene therapy except one.
a. Parkinson's disease
b. Diabetes
c. Multiple myeloma
d. Leber's congenital amaurosis
5. Who does not approved gene therapy yet?
a. FDA
b. ADA-SCID
d. DFA
c. WHO

19. Post-Test
6. When was the first gene therapy performed?
a. September 14, 1902
b. September 14,1990
c. September 14, 1995
d. September 14, 1972
7. Who was the first person that was treated by gene therapy?
a. Jesse Gelsinger
b. Ashenti DeSilva
c. Ashanti DeSilva
d. Jesse Gilsinger
8. These are the problems encountered in gene therapy except one.
a. Short life span
b. Viral Vectors
c. Multigene Disorders
d. Fever
9. It replaces a faulty gene or adds a new gene in an attempt to cure disease or improve your
body's ability to fight disease?
a. Miracles
b. Gene therapy
10. What do you mean by SCID?
a. Severe Combined Immunodeficiency
b.Surgical Combined Immunodeficiency
c. Herbal
d. Medicines
c. Severe Common Immunodeficiency
d. Stone Cloning Immunodeficiency

20. Enrichment:
Direction: Fill in the Blanks.
1.Gene therapy can use ____ to insert genes that encode for a desired
protein to create the desired trait.
2.The ____________ goes through reverse transcription using reverse
transcriptase and RNA.
3.____________ is from parvovirus family- causes no known disease and
doesn't trigger patient immune response.
4.__________ is a cancer that begins in developing blood cells in the
bone marrow.
5.___________ is a tool commonly used by molecular biologists to
deliver genetic material into cells. This process can be performed inside
a living organism or in cell culture.
6.____________ is a gene therapy patient who lacked ornithine
transcarbamylase activity, died in 1999.
7.The first gene therapy was performed on ___________________.
8.__________________is a double stranded DNA virus that infects
neurons.

21. Jumbled letters:
Direction: Give the exact word of the jumbled letter to form a new
word and described each..
1. ANODESVRIU
2. EGNE
3. LECL
4. NEZYSM
5. SEPHER IMSXELP SUVIRES
6. SURVIES
7. GEEITNC NENRININGEEG
8. RAVIL SRTVCEO
9. TREORSUVIESR
10. EULIAMKE

22. Crossword puzzle:
Direction: Find the following
words in the puzzle either
horizontal, vertical, diagonal and
even upside down.
V
V
A
L
E
U
K
E
M
I
A
F
M
I
S
S
F
G
X
C
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A
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G
O
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U
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E
U
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C
D
J
K
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E
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I
T
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E
M
Y
Z
N
E
B
C
E
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H
L
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A
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N
U
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U
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D
Y
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A
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O
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O
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H
D
G
S
X
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P
O
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K
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B
M
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V
F
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Words to find:
1. Virus
2. Cell
3. Carrier
4. Retrovirus
5. Enzymes
6. Leukemia
7. Clone
8. Molecules
9. Mutations
10. Protein

23. Answer Key:
Pre-Test and
Post-Test Key:
1. A
2. C
3. B
4. B
5. A
6. B
7. C
8. D
9. B
10. A
4 pics, 1 word
Key:
1. Gene Therapy
2. Cell
3. Genetic
Engineering
4. Leukemia
5. Viral Vectors
6. Retrovirus
7. Adenoviruses
8. Carrier
9. Enzymes
10. Clone
Enrichment Key:
1. Viruses
2. Retrovirus
3. Adeno-associated
Viruses
4. Leukemia
5. Viral Vectors
6. Jesse Gelsinger
7. September 14th,
1990
8. Herpes Simplex
Viruses
9. 1980
10. Gene

24. Answer Key:
Jumbled Letters: Any of the answer below.
Adenovirus- is double stranded DNA genome that cause respiratory, intestinal, and eye
infections in humans. The inserted DNA is not incorporate into genome.
Gene- The basic unit of heredity. Proteins carry out most of life’s function. When altered
causes dysfunction of a protein.
Cell- It is the basic structural, functional and biological unit of all known living organism. The
smallest unit of life that is classified as a living thing, and are often called the "building blocks
of life".
Enzymes- A protein that facilitates a specific chemical reaction.
Herpes Simplex Virus- Double stranded DNA viruses that infect neurons
Virus- Replicate by inserting their DNA into a host cell. Gene therapy can use this to insert
genes that encode for a desired protein to create the desired trait.
Genetic Engineering- Also called genetic modification is the direct manipulation of an
organism's genome using biotech.
Viral Vectors- A tool commonly used by molecular biologists to deliver genetic material
into cells. This process can be performed inside a living organism or in cell
culture.
Retrovirus-Created double stranded DNA copies from RNA genome
Leukemia- A malignant progressive disease in which the bone marrow and other
blood-forming organs produce increased numbers of immature or
abnormal
leucocytes. These suppress the production of normal blood cells,
leading to
anemia and other symptoms.

25. Answer Key:
Crossword Puzzle:

26. Acknowledgemen
t:
As we start this project, we have all the courage we need, to do
our best for this. And we give thanks to everyone behind our SIM.
First and foremost we want to thank Ma’am Lim, our Biotechnology
teacher for giving this project to us and letting us work as a group. Choz.
Then to our parents who are helping us financially to fulfill this project
especially to Aubrey’s ever loving and supportive mother for binding all the
papers. To the internet who
never fails to sustain our
needs about gene therapy
and to make it understandable and
clear. Choz. For the
members composing the group, Aubrey,
Jairra, Mikah,
Neil and Yllian. We couldn’t finish this without all our
cooperation. And lastly, to our glorious and merciful
God for giving us the allotted time to work on this
project and giving us the wisdom to manage and think of
ideas for
this SIM. We’re hoping that you’ll enjoy and l earn gene therapy clearly.
—Miracle Therapists 

27. Bases:





Burdette, Walter J. The Basis for Gene Therapy. Springfield: Charles
C
Thomas, 2001.
Crayton, Stephanie. “First Clinical Trial Of Gene Therapy For Muscular
Dystrophy Now Under Way.” Medical News Today. 1 April 2006. University of
North Carolina at Chapel Hill. 11 November 2006
<www.medicalnewstoday.com>.
Gene Therapy. Human Genome Project Information. 18 November
2005. U.S. Department of Energy Office of Science, Office of
Biological
and Environmental Research, Human Genome
Program. 12
September 2006 <http://www.ornl.gov/hgmis>.
McCormack, Matthew P. “Activation of the T-Cell Oncogene LMO2
after Gene Therapy for X-Linked Severe Combined
Immunodeficiency.”
The New England Journal of Medicine.
http://content.nejm.org. 346:
1185-1193, Apr 18, 2002.
Peel, David. “Virus Vectors & Gene Therapy: Problems,
Promises &
Prospects.” Virus Vectors & Gene
Therapy.
1998. Department
of Microbiology & Immunology, University of
Leicester. 11 November
2006
<http://www.tulane.edu/
~dmsander/WWW/335/peel/peel2.html>.