2. GENE THERAPY
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.
The technique was first developed in 1972 but has, so far,
had limited success in treating human diseases.
3. Gene therapy replaces a faulty gene
or adds a new gene in an attempt to
cure disease or improve your body's
ability to fight disease. Gene therapy
holds promise for treating a wide
range of diseases, such as cancer,
cystic fibrosis, heart disease,
diabetes, hemophilia and AIDS.
Researchers are still studying how and when to use gene therapy.
Currently, in the United States, gene therapy is available only as
part of a clinical trial.
4. HISTORICAL ASPECTS
The concept of manipulating genes to treat diseases
has been a dream of scientists for decades.
-The initial steps in gene therapy research were taken
in the 1970s and 1980s, but it wasn't until the 1990s
that the first clinical trials began, marking a pivotal
moment in medical history.
Over the years, the field has witnessed remarkable
advancements, from developing safer delivery
mechanisms to expanding the range of treatable
diseases.
5. 1 IMMUNE DEFICIENCIES - Several inherited immune deficiencies
have been treated successfully with gene therapy. Most commonly,
blood stem cells are removed from patients, and retroviruses are used to
deliver working copies of the defective genes.
Adenosine deaminase (ADA) deficiency is
another inherited immune disorder that has
been successfully treated with gene therapy. In
multiple small trials, patients' blood stem cells
were removed, treated with a retroviral vector to
deliver a functional copy of the ADA gene, and
then returned to the patients.
6. Several promising gene-therapy
treatments are under development for
cancer. One, a modified version of the
herpes simplex 1 virus, has been shown to
be effective against melanoma (a skin
cancer) that has spread throughout the
body. The treatment, called T-VEC, uses a
virus that has been modified so that it will
(1) not cause cold sores; (2) kill only
cancer cells, not healthy ones; and (3)
make signals that attract the patient's own
immune cells, helping them learn to
recognize and fight cancer cells
7. PARKINSON'S
DISEASE
Patients with Parkinson's disease gradually lose cells in the
brain that produce the signaling molecule dopamine. As the
disease advances, patients lose the ability to control their
movements.
A small group of patients with advanced Parkinson's disease
were treated with a retroviral vector to introduce three genes into
cells in a small area of the brain. These genes gave cells that
don't normally make dopamine the ability to do so.
Other disease treatments include HAEMOPHILIA , BLOOD
DISEASES, HEREDITARY BLINDNESS ETC.
8. Types of gene alterations - it mainly involves three stages,
namely, addition, inhibition, editing (functional replacement
of a gene).
Gene addition
It involves the introduction of a new gene into the body to target a
specific aspect of what causes the disease.
Gene inhibition
Gene inhibition involves deactivating or “silencing” the expression of
a mutated or faulty gene that codes for a toxic protein or too much
protein.
9. Gene editing
The mutant gene that is causing disease is edited in order to
correct the mutation. This technique aims to repair the altered
gene by inserting, removing, or changing specific pieces of a
person's existing DNA.
Gene replacement
Gene replacement is a way to treat genetic diseases. It
replaces the function of a missing, faulty, or nonworking gene
with a new, working copy of the malfunctioning gene.
Because gene replacement delivers a new, working gene to the
body, it has the potential to help people with monogenic
diseases.
10. VECTORS
Vectors are the delivery vehicles used to carry a new,
working copy of the missing or nonworking gene into the right
cells inside the body. Viruses are used because they are very
good at getting inside of cells and carry the new working
genes into the nucleus of the cell. Viruses commonly studied
for use as viral vectors in gene therapy include
retroviruses,
adenoviruses,
adeno-associated viruses (AAVs),
lentiviruses.
AAVs have been approved for use in gene therapy. AAVs are
not known to cause illness in people and have demonstrated
safety in clinical trials.
11.
12. 1) CREATING A WORKING GENE The gene transfer therapy involves
creating a working (or functional) gene in the laboratory.
2) Building a therapeutic vector - The working gene now has to
be delivered into the body. The shell of the virus is created without
the viral DNA and working gene is put inside the empty shell.
3) Delivering the working gene - A single, one time infusion in an
appropriate clinical sting delivers large number of therapeutic vectors into the
body. The therapeutic vectors are designed to both protect and guide the
working gene toward preferred cells where it can be used to make the
needed protein
4) Monitoring safety and efficacy- to understand any risk and what
impact the gene transfer is having
13. .
TYPES OF GENE THERAPIES
There are two different types of gene therapy depending on
which types of cells are treated:
Germline gene therapy - Germline therapy involves the
modification of the genes inside germ or gamete cells,
which include sperm or ova.
Germline therapy would therefore be administered
during reproduction, the zygote passes on the modified
gene to all other cells of the body during the
development of offspring.
germline therapy alters the genome of future
generations to come.
14. Somatic Gene therapy
Unlike germline therapy, somatic
gene therapy involves the insertion
of therapeutic DNA into body cells,
rather than germ cells or gametes.
This means that any effects of the
therapy are confined to the
individual being treated and are not
inherited by future offspring
15. WAYS OF GENE THERAPY
The two major approaches in delivering the
gene are
1) in vivo gene therapy
2) ex vivo gene therapy
IN VIVO - In vivo gene therapy
refers to direct delivery of
genetic material either
intravenously (through an IV)
or locally to a specific organ
(eg, directly into the eye)
16. EX VIVO
Ex vivo gene therapy refers
to the process of removing
specific cells from a person,
genetically altering them in
a laboratory, and then
transplanting them back
into the person
17. APPLICATIONS AND ACHIEVEMENTS
Conditions like spinal muscular atrophy (SMA), hemophilia, and
inherited retinal diseases that were once considered incurable are
now within the possibility for effective treatment.
Moreover, the field of cancer immunotherapy, subset of gene
therapy, uses the immune system's power by genetically
modifying T cells to specifically target and destroy cancer cells.
Excitingly, ongoing research is exploring the potential of gene
therapy to combat neurodegenerative diseases, including
Alzheimer's and Parkinson's, promising a brighter future for those
affected .
The horizon of possibilities in gene therapy continues to expand.
18. CHALLENGES AND RISKS FACED
Delivering the gene to the right place and switching it on delivering
a gene into the wrong cell would be inefficient and could also
cause health problems for the patient.
Avoiding the immune response: Sometimes new genes introduced
by gene therapy are considered potentially-harmful intruders.
Making sure the new gene doesn’t disrupt the function of other
genes: 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. There is a risk that the new gene will
insert itself into the path of another gene, disrupting its activity.
19. Challenges , cont..
The cost of gene therapy:
Many genetic disorders that can be targeted with gene therapy
are extremely rare.
Gene therapy therefore often requires an individual, case-by-
case approach. This may be effective, but may also be very
expensive.
Commercial viability - Developing a new therapy—including
taking it through the clinical trials necessary for government
approval— is very expensive. With a limited number of patients
to recover those expenses from, developers may never earn
money from treating such rare genetic disorders. And some
patients may never be able to afford them.
20. ETHICAL CONSIDERATIONS
While gene therapy holds immense promise, it is not without its
set of challenges and ethical dilemmas. Concerns about off-
target effects and immune responses necessitate meticulous
research and testing to ensure the safety and efficacy of gene
therapies.
Ethical discussions surrounding germline editing, the potential
for unintended consequences, and the need for responsible
genetic manipulation are ongoing, highlighting the importance of
a balanced approach to this groundbreaking technology.
21. CONCLUSION AND MY PERSPECTIVE
Gene therapy's potential to revolutionize medicine is
undeniable. As research continues to advance and ethical
considerations evolve, we find ourselves at the threshold of
a new era in healthcare.
I strongly accept the use of gene therapy But I believe that there should
be safeguards put into place in order to avoid abuse of gene therapy
leading to the creation of a ‘super race’. It could improve the quality and
spam of life of people suffering from these disorders
Overall, I fully believe that this technology could result in great
advancements and benefits for society however it could present dangers
of misuse which through proper regulation can be prevented.
