2. Gene
Gene Therapy
Approaches for gene therapy
History
How gene therapy is carried out?
How it works?
Delivery systems
Different types of viruses used in gene therapy
vectors
3. Non-viral Options
Disadvantages of gene therapy
Disease targets for Gene Therapy
oImmunodeficiency disorder
oVascular proliferative disorders
oLung Diseases
oLiver diseases
oSkeletal muscle
oHemoglobinopathies
oCancer
oOthers
oRare Disease Treated Using Gene
Therapy
4. GENES
Carried on chromosome
Basic unit of hereditary
Encode how to make protein
DNA>RNA>Protein
When gene altered cause
dysfunction of a protein
5.
6. GENE THERAPY
It is technique for correcting defective
genes that are responsible for disease
development
Introduction of normal gene into cells
that contain defective gene to
reconstitute a missing protein product
Is used to correct a definitive
phenotype so that sufficient amount of
a normal gene product are synthesized
7. Approaches for 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
Change the regulation of gene pairs
8. HISTORY
In 1980’s scientists began to look
into gene therapy
Insert human gene to bacterial cell
Bacterial cell would transcribe and
translate the information into protein
Then they would introduce the protein
into human cells
9. HOW GENE THERAPY IS CARRIED
OUT?
Modification of somatic cell by
transferring desired gene sequence
into the genome
Somatic cell necessary to ensure
that inserted genes are not carried
over to the next generation
10. How it works?
A vector delivers the therapeutic gene
into a patient’s target cell
The target cell become infected with the
viral vector
The vector’s genetic material is
inserted into the target cell
Functional protein are created from the
therapeutic gene causing the cell to
return to a normal state
11.
12.
13. Delivery systems
In vivo:-
o Delivery of gene takes place in
the body
In vitro:-
o Delivery takes place out of the
body and then cell are placed
back into the body
14. In vivo technique use viral vector:-
– Virus = carrier of desired gene
– Virus is usually “crippled” to disable its
ability to cause disease
– Viral methods have proved to be the
most efficient to date
– Many viral vectors can stable integrate
the desired gene into the target cell’s
genome
15. In vitro technique usually use
manipulation technique:-
– Electroporation
– Liposome
– Calcium phosphate
– Gold bullets (fired within helium pressurized
gun)
– Retrotransposons (jumping genes – early
days)
– Human artificial chromosomes
16. Different types of viruses used in
gene therapy vectors
Retroviruses:-
A class of viruses that can
create double standard DNA
copies of their RNA genome
Copy of its genome can be
integrated into the chromosome
of host cell
HIV virus is retrovirus
17.
18. Adenovirus:-
A class of viruses with double
standard DNA genome that
cause respiratory, intestinal,
and eye infection in human
Virus that cause common cold
is adenovirus
19. Adeno- associated virus:-
A class of small, single,
standard DNA viruses that can
insert their genetic material at a
specific site on chromosome 19
20. Herpes simplex virus:-
A class of double standard DNA
viruses that infect a particular
cell type, neurons
21. Non-viral Options
Direct introduction of therapeutic
DNA into target cells
The creation of an artificial lipid
sphere with an aqueous core
Chemically linking the DNA to a
molecule that will bind to special cell
receptors (less effective )
22. Advantage of gene therapy
Provide better treatment options for
cancer, AIDS and some hereditary
disease
23. Disadvantages of gene therapy
Short-lived nature of gene therapy
Immune response
Problems with viral vectors
Multigene disorders
Ethical and legal problems
Religious concerns
24. Disease targets for Gene Therapy
Immunodeficiency disorder :-
For the treatment of congenital
immunodeficiency disorder
illustrate the use of ex vivo gene
transfer into hematopoietic stem cell
The three important
immunodeficiency syndrome that
use gene therapy are:-
25. Adenosine deaminase deficiency:-
o First genetic diseases clinically treated
with gene therapy
o In children with this disorder leads to
the accumulation of deoxyadenosine
triphosphate that is toxic to lymphocyte
o It develop infections due to the
defective cell mediated and humoral
immune responses
26. Standard therapy is bone marrow
transplantation with periodic infusion of
PEG-ADA enzyme
27. X- linked severe combined
immunodeficiency:-
Gene therapy for treating children with
X-SCID (sever combined
immunodeficiency) or the "bubble boy“
Child is born with a very weal immune
system
Through this therapy, ADA is inserted
and then the genetically corrected cells
are transplanted back into the child
28. Vascular proliferative
disorders
Atherosclerosis, restenosis after
angioplasty, and bypass-graft failure,
are leading causes of morbidity and
mortality
Leads to up-regulated expression of
growth factors, cytokines, and
adhesion molecules by the vascular
smooth-muscle cells
29.
30. Lung Diseases
Several gene delivery vectors have
been applied to treating inherited
lung diseases
Cystic fibrosis:-
Adeno-associated viral vector for
delivering CFTR are now in clinical
trials
31. Alpha-1 Antitrypsin deficiency:-
It cause individual to pulmonary
emphysema and hepatic chirriosis
Recombinant alpha-1 antitrypsin
protein is commercially available for
human use
32. Liver diseases
The liver can be afflicted with variety
of metabolic, infectious, and
neoplastic diseases for which
specific molecular intervention can
be envisioned
33. Skeletal muscle
A variety of inherited disorder of
muscle including Duchenne
muscular dystrophy and the limb
girdle muscular dystrophies are
prime targets for the development of
gene based therapies
Adeno- associated virus has been
demonstrated to be capable of
efficient and stable transduction of
adult skeletal muscle
34. Hemoglobinopathies
Sickle cell disease and the
thalassemias are common single
gene disorders associated with
substantial morbidity and mortality
These disorder should be amenable
to ex vivo gene transfer into
hematopoietic stem cells which then
would be used to reconstitute a
patient’s bone marrow
35. Cancer
Multiple strategies have been
experimented with to treat different
kinds of cancer.
These strategies include:-
Oncolytic virotherapy
Suicide gene therapy
Therapeutic gene vaccines
Anti-angiogenesis
36. Nanotechnology + gene therapy
yields treatment to torpedo cancer.
A combination of two tumor
suppressing genes delivered in
lipid-based nanoparticles
drastically reduces the number
and size of human lung cancer
tumors
37. Others
Chronic Granulomatus Disorder
(CGD),in which the process of ADA-
SCID is followed to help the patients
In Hemophilia, the therapeutic gene
is introduced in the patient’s body to
cure it.
38. Gene therapy is effectively used to
treat two adult patients for a disease
affecting no lymphocytic white blood
cells called myeloid cells
Gene Therapy cures deafness in
guinea pigs. Thus gene therapy cure
deafness
41. Brain scans of two boys with X-
linked adrenoleukodystrophy (ALD):-
The scans on the left (A) are from
a patient who received gene
therapy
the one on the right (B) did not
The white areas represent the
brain damage caused by the
disease
42. The arrow on the left points to an
area that showed some damage,
but receded over the course of the
therapy
When gene therapy started, there
were a lot of predictions that this
was going to revolutionize
medicine. It's been a long time to
actually get it to work in humans"
43. If the treatment for ALD holds up, it
might be the start of that revolution
