Topic 11: The Aspects of Gene Therapy

Learning Objectives
After successful completion of this module, you should be able to:

• Describe gene therapy and its related processes;

• Compare and contrast vectors of gene delivery; and
• Enumerate the pros and cons of gene therapy in the society.

Activating Prior Knowledge

Learning Activity: W-O-R-D-U-P

Directions: Using the grid below, find words related to gene therapy. You may
use the statements that follow as your clues to identify the words. Write your
answer on the space provided after each statement.

E Q Z X L E L L Q S T Y C W M

C G V C H T S I P K I K I U E

G O E B K H U N T I N G T O N

V L C R H O R U F H R A A N I

V W T Y M P I H C E T U M R O

J Q O K A L V F L I T E O R T

B L R L U L I R D W E T S E A

O E S M T T A N Q N T Y U O I

L S I C K L E C E L L A N E M

P S V E O U Q G A A E I O Z P

1. A disorder of the nervous system that usually occurs after the age of
45. WILSON DISEASE
 2. A disorder in the blood caused by an inherited abnormal hemoglobin (the
oxygen-carrying protein within the red blood cells). SICKLE CELL
3. Are plasmid or viruses that are used to move recombinant DNA from one
cell to another HERPES
4. Is the alteration of the nucleotide sequence of the genome of an
organism, virus or extrachromosomal DNA. MUTATION
5. A unit of DNA that is usually located on a chromosome and that controls
the development of one or more traits. GENE
6. Gene therapy that targets the reproductive cells meaning any changes
made to the DNA will be passed on to the next generation. GERMLINE
7. It is when the DNA is transferred into body tissues. It specifically targets
cells in the body which are not passed on to the person’s
children.SOMATIC_

Presentation of Contents

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.

Two Types of Gene Therapy

Somatic gene therapy, which involves introducing a "good" gene into

targeted cells to treat the patient — but not the patient's future children
because these genes do not get passed along to offspring.
Germline gene therapy, involves the introduction of corrective genes into
reproductive cells (sperm and eggs) or zygotes, with the objective of creating
a beneficial genetic change that is transmitted to the offspring.

Gene Therapy Using Adenovirus Vector

A new gene is inserted directly into a cell. A carrier called a vector is

genetically engineered to deliver the gene. An adenovirus introduces the
DNA into the nucleus of the cell, but the DNA is not integrated into a
chromosome.

Vectors for Gene Delivery

Appropriate methods to deliver DNA used in gene therapy are vital, as the
targeted tissues must properly receive the appropriate genes. Gene therapy
can be carried out using naked DNA delivered directly into the cell.
 (Source: www.biologydiscussion.com)
Fig: 9.1 Structure of Adenovirus

Adenoviruses - are a group of common viruses that infect the lining of your
eyes, airways and lungs, intestines, urinary tract, and nervous system.
They're common causes of fever, coughs, sore throats, diarrhea, and pink
eye.

Source: www.andrew.cmu.edu
Fig: 9.2 Structure of Retrovirus

Retrovirus is a type of RNA virus that inserts a copy of its genome into the DNA
of a host cell that it invades, thus changing the genome of that cell.
 Source: http://m.wikipedia.org
Fig. 9.3 Structure of Adeno-associated virus

Adeno-associated virus (AAV) - is a non-enveloped virus that can be

engineered to deliver DNA to target cells, and has attracted a significant
amount of attention in the field, especially in clinical-stage experimental
therapeutic strategies.

(Source: https:// study.com)

Fig. 9.4 Structure of Herpes Simplex
Herpes simplex type 1 causes sores around the mouth and lips (sometimes
called fever blisters or cold sores). HSV-1 can cause genital herpes, but most
cases of genital herpes are caused by herpes type 2. In HSV-2, the infected
person may have sores around the genitals or rectum.

Source: library.open.oregonstate.edu
Fig. 9.5 Structure of Naked DNA

Naked DNA refers to DNA that is not associated with proteins, lipids, or any
other molecule to help protect it. Naked DNA is the result of release of
genetic information into the surrounding environment, such as from bursting
cells.

Bioethical Issues of Gene Therapy

The first death associated with gene therapy occurred on September 18,
1999, at the University of Pennsylvania. Jesse Gelsinger was participating in
a clinical trial, a biomedical experiment for evaluation of safety and
efficiency of a therapy for a disease. Gelsinger, who was 18 years old at the
time of the treatment, had a deficiency of ornithine transcarboamylase, an
important enzyme in the metabolism of ammonia. Patients with this rare
metabolic disorder must maintain a low-protein diet and take a series of
medicines to avoid ammonia poisoning in the blood stream. The gene
therapy Gelsinger took triggered a chain reaction in his immune system,
resulting in hepatic and respiratory failure, and consequently, his death four
days after being treated.
Effects on the Environment

Although the positive impacts of gene therapy could be enormous, there are
many questions raised that needs to be answered. New organisms created by
genetic engineering could present an ecological problem. One cannot predict
the changes that a genetically engineered species would make on the
environment. The release of a new genetically engineered species would also
have the possibility of causing an imbalance in the ecology of a region just
exotic species would do. An accident or an unknown result could cause
several problems. An accident in engineering the genetics of a virus or
bacteria for example could result in a stronger type, which could cause a
serious epidemic when released. This could be fatal in human genetic
engineering creating problems ranging from minor medical problems, to
death.

Effects on Human

Looking at the fact that genetic engineering employs viral vector that carries
functional gene inside the human body; the repercussion are still unknown.
There are no clues as to where functional genes are being placed. They may
even replace the important genes, instead of mutated genes. Thus, this may
lead to another health condition or disease to human. Also, as defective
genes are replaced with functional gene, then it is expected that there will be
a reduction in genetic diversity and if human beings will have identical
genomes, the population as a whole will be susceptible to virus or any form
of diseases.

Antibiotic Resistance

Genetic engineering often uses genes for antibiotic resistance as "selectable

markers." Early in the engineering process, these markers help identify cells
that have taken up foreign genes. Although they have no further use, the
genes continue to be expressed in plant tissues. Most genetically engineered
plant foods carry fully functioning antibiotic-resistance genes.

The presence of antibiotic-resistance genes in foods could have lethal effects.

Therefore, eating these foods could reduce the effectiveness of antibiotics to
fight disease when these antibiotics are taken with meals. More so, the
resistance genes could be transferred to human or animal pathogens, making
them impervious to antibiotics. If transfer were to occur, it could aggravate
the already serious health problem of antibiotic resistant disease organisms
Ethical and Social Issues

"Playing God" has become a strong argument against genetic engineering.

Several issues have also been raised as regards the acceptance of this
technology. These concerns range from ethical issues to lack of knowledge
on the effects genetic engineering may have. One major concern is that once
an altered gene is placed in an organism, the process cannot be reversed. The
production of medicines through the use of genetically altered organisms
might develop extremely infectious forms that could cause worldwide
epidemics.

Application

Activity 1: What genes are you wearing?

Choose one of the following diseases.

• HIV • Cystic fibrosis • Hemophilia

• Muscular dystrophy • Rheumatoid arthritis • Coronary heart disease

• Alzheimer’s disease • Ulcer • Bone fracture

• Cancer • Sickle cell anemia •Huntington’s disease

• Tay-sach's disease

Each one of you will choose “What Genes are you Wearing?” packet that is
tailored to the disease chosen. You will present your output regarding the topic you
have chosen and you will answer the following questions.

I choose "Cancer"

1. Is gene therapy safe to cure genetic disorder?

 Answer: According to research, It is not hundred percent sure that it is
really safe. It still have a lot to prove and it might cause some serious
health risk, including cancer. The researchers are still trying it out. So no,
it is not yet safe. Further studies are still needed for one to say It's safe.

2. If you are the patient suffering from a genetic disease are you willing to undergo
gene therapy? Why?

Answer: No, why would I risk my health for something unsure. There is a
chance that I will be going to be cured but so is getting more severe.
Maybe when further studies already proved that it really is safe and it
really cures my disorder, I'll be willing to undergo. It is genetic, my other
relatives might found some safe alternatives to cure theirs so I'm sure I
will be going to use it instead of this unsure therapy.

Activity 2: Vector Voyage

Direction: Using the library resources, complete the table below.

Retrovirus Adenovirus Adeno- Herpes Naked

associated Simplex DNA
Virus Virus
How the In the form of DNA dsDNA (oral Lone,
vector carries RNA; most (common ssDNA (do &genitalhers) circular
the genetic famous is HIV; cold) not cause VIRAL dsDNA
material affects only illness in (plasmid); not
dividing cells VIRAL humans) packaged

VIRAL VIRAL NON

VIRAL
Maximum
length of DNA 8,000 bp 7,500 bp 5,000 bp 20,000 bp No max
that can be length
inserted in the
vector

Affect Enters into Target & Nonspecific

diving & cells easily; infect cells of to cells;;
Advantages Contains non- dividing affect wide nervous Once inside a
enzyme to cells; Once range of system, Once cell, plasmid
convert RNA to adenovirus diving & not it infects a DNA is
DNA before infects cell, dividing cell, DNA transported
genes can be
DNA travels cells; Once it travels to the to nucleus
activated; DNA
to cell affects a cell, nucleus and where genes
will integrate
nucleus DNA travels activates are activated;
into host cell's
genome @ immune to nucleus genes; DNA Best suited
random response you where its will stay in for ex vivo
locations; Will can remove genes are cell's nucleus gene therapy
duplicate when the proteins activated; for a long approaches
the cell divides on the will time as a
surface that integrate separate
trigger it virus DNA circular piece
into host of DNA that
genome replicates
(95% of the with cell
time in the division; Will
same not disrupt
location on function of
chromo 19, other genes in
reducing the cell;
disruption
of other
genes)
Might disrupt Immune Need a DNA will not Enters cells
cell's genome if responses can "Helper" integrate into less effectively
Disadvantages DNA is inserted prevent virus to genome; Will than virus;
into random sustained replicate cause an Unless
spot; Might usage; themselves immune engineered to
affect cell Effective inside cells; response (can do so, plasmid
division-causing temporary; Will not remove DNA will not
tumor growth; DNA will not cause an proteins from integrate into
May cause an integrate into immune surface to cell's genome
immune host cells response eliminate (even if
response- genome (after response) engineered,
solution= a week or two effectiveness

Activity 3: GENETIC DISORDERS
Direction: Complete the table below. List down ten common genetic disorders.
GENETIC DISORDER
Haemophilia
Apert syndrome.
Ankylosing spondylitis
Reduce the cell will
possibility of discard it &
response by gene
removing activation
proteins on lost)
surface of virus
that trigger it
GENE/DEFECT
When a blood vessel is
Injured, special proteins in
the blood called "clotting
factors' act to control blood
loss by plugging or patching
up the injury. People with
haemophilia have lower than
normal levels of a clotting
factor.
Mutations in a gene known as
fgfr2 cause apert
syndrome.This gene provides
instructions for making a
protein called
fibroblast growth factor
receptor 2 Among its
multiple functions, the fgfr2
protein plays a key role in
development before birth by
signaling immature cells to
become bone cells.
• A variation of the hla b gene
called hla-b27 increases the
risk of developingankylosing
is low); Will
not generate
an immune
response;
CLINICAL FEATURES
• easy bruising from an early
age
• Internal bleeding for no
obvious reason, especially in
the joints and muscles
• greater than normal
bleeding following injury or
surgery abnormally heavy
bleeding
• during menstruation or after
giving birth
Tall skull and high prominent
forehead. Underdeveloped
upper jaw. Prominent eyes
that appear to be bulging out
and may be spaced widely
apart. Small nose.
• Early signs and symptoms
of ankylosing spondylitis
might include pain and
 spondylitis. Although many
people with ankylosing
spondylitis have the hla-b27
variation, most people with
this version of the hla-b gene
never develop the disorder.
Duchenne Muscular • Muscular dystrophy is a
Dystrophy condition that causes
progressive wasting of the
muscles. Duchenne muscular
dystrophy is a particular type
of muscular dystrophy caused
by a mutation in the DMD
gene. It affects more boys
than girls.
The DMD gene helps
produce a protein called
dystrophin, which is
important for muscle
strength, support and repair.
People with Duchenne
muscular dystrophy don't
produce the normal form of
dystrophin, which means
their muscles are more easily
damaged and don't work
properly.
The genetic mutation of the
DMD
Huntington • Huntington's disease is an
autosomal dominantdisorder.
which means that a person
needs only one copy of the
defective gene to develop
thedisorder. With the
exception of genes on the sex
copy from cach parent.
stiffness in your lower back
and hips, especially in the
morning and after periods of
Inactivity. Neckpain and
fatigue also are common.
Over time, symptoms might
worsen, improve or stop at
irregular intervals.
• The first thing parents
usually notice is that their
child isn't reaching their
motor (muscle movement)
milestones. They might also
notice that their child falls
over often. Is clumsy and
walks on their toes.
Later, the child with
Duchenne muscular
dystrophy might develop:
• muscle weakness that
affects their posture, walking
and running
• reduced joint movement due
to shortening of their muscles
• problems with
• Involuntary jerking or
writhing movements (chorea)
Muscle problems, such as
rigidity or muscle contracture
(dystonia)
Slow abnormal eye
movements. Impaired galt,
 chromosomes, a person
Inherits two copies of every
gene-one
Albinism • Albinism (oca)-a group of
inherited disorders where
there is little or no production
of the pigment melanin. The
type and amount of melanin
your body produces
determines the color of your
skin, hair and eyes.
Angelman syndrome • Angelman syndrome is
caused by a loss of function
of a gene called ube3a
onchromosome 15. The exact
mechanism that causes this
loss of function is complex.
People normally inherit one
copy of the ube3a gene from
each parent. Both copies of
this gene are turned on
(active) in many of the body's
tissues.
Down syndrome •People who inherit an
unbalanced translocation
. Ehlers-Danlos Syndrome • Ehlers-Danlos syndrome is
a genetic condition that
mainly affects the joints and
skin and walls of the blood
vessels
posture and.balance.
Difficulty with speech or
swallowing.
• Albinism occurs with vision
problems, which may
include: Strabismus (crossed
eyes) Photophobla
(sensitivity to light)
Nystagmus (involuntary rapid
eye movements) Impaired
vision or blindness.
Astigmatism.
• Delayed development,
intellectual disability, severo
speech impairment, and
problems with movement and
balance (ataxia).
• Flattened face. Small head.
• There are many different
types. of EDS. All of them
involve extremely flexible
joints and fragile skin that
bruises and stretches easily.
Ehlers-Danlos syndrome is a
genetic condition that mainly
affects the joints and skin and
walls of the blood vessels
People who inherit an
unbalanced translocation
Some find their joints are so
flexible that they have
frequent. dislocations, and

Tourette Syndrome
Activity 4: Pros and Cons
Fill out the table below by describing the pros and cons of gene therapy.
• Tourette syndrome, or TS, is
an inherited neurological
disorder that causes people to
make involuntary and
uncontrollable vocal sounds
and movements,
called 'tles'. Recent research
suggests that a small number
of Tourette syndrome cases
may be caused by a defect on
chromosome 13 of gene
SLITRKI. Some cases of
tourettism (tics due to reasons
other than inherited Tourette's
syndrome) can be caused by
mutation.
this often leads to pain in the
joints.
Some people with EDS have
distinctive facial features
such as a thin nose, thin
upper lip, large eyes and ears
without lobes.
• Tourette syndrome
symptoms are usually mild,
but can i sometimes be
severe.
One set of symptoms is
known as movement tics.
People with movement tics
can find themselves jerking
their head, stretching their
neck, stamping their feet, and
twisting and bending. Some
people may bite themselves
or hurt themselves in other
ways, or find it necessary to
repeatedly touch other people
and things.
Another set of symptoms is
known as vocal tics. People
with vocal tics might clear
their throat, cough, sniff,
click their tongue, grunt,
yelp, bark.or shout. Some
also swear or repeat certain
sounds or phrases.
 Pros Cons

• It can cure • It is very

genedisorders and dangerous and
Human Health improve risky to the patient
the body's ability to who will undergo
fight/prevent the with this kind of
disease treatment

• The genes would •Having a Long-

allow to passed in the term side effect in
Society Future. generations. every individual
who has carrier of
this genes

Guide Questions:

1. What was the respondent think about gene therapy?

Answer: > Many think this type of treatment will heal and cure every person who has the
disease's genetic disorder, and some people do not like this because it has a large number of side
effects.

2.)Do you think the Food and Drug Administration should or should not approve gene therapy
treatments for use in the Philippines?

Answer: > For my opinion. Food and Drug Administration will or should approve this because
in the other country like US they used this kind of therapy treatment to cure the disease even if
it cost a lot. Some people are relying on the treatments to heal their illnesses.

3.)Do you think the government should or should not fund scientific researches on changing the
genes of unborn babies that aims to improve their characteristics such as intelligence or physical
traits such as athletic ability or appearance.

Answer:: In my opinion, the government should fund scientific researchers who are working on
changing the genes of unborn babies in order to improve their characteristics. such as
intelligence or physical traits such as athletic ability or appearance, because it will be beneficial
for every individual to be born in the future generation and have a good life. And it does not
violate any proposed legislation in the country.

Feedback

What does the picture show?

Source: www.tutorialspoint.com
for me ma'am the picture show explain the important work of Disease Intervention Specialists and
others who perform contact tracing for STDs. The infographic is meant to be an easy visual to explain this
hard boots-on-the-ground work done by member health departments across the county!

The hope is that when those that hold the purse strings better understand the essential work that is
done through contact tracing, there may be more support for these programs. plans to use this
infographic to show policymakers how contact tracing for STDs functions and explain how they are
pulled into emergency response situations and the impact that has on STD prevention and treatment

and also Improving Patient Safety Through Healthcare Interoperability

Achieving widespread healthcare interoperability should prove instrumental to reducing opioid-related

overdoses and medical errors.