it's for alllll

1. Gene Therapy
and it’s application in
Cancer,
HIV and Hereditary
diseases
BY:
Md. Monirul Islam
Pharmacy Discipline
Khulna University
Khulna.

2. Gene Therapy An Overview
Background
Gene therapy is “the use of genes as medicine”. It involves the
transfer of a therapeutic or correct gene into specific cells of an
individual in order to repair a faulty gene.
1980
• Advances in sequence & cloning of human gene.
1990
• Ashanti De Silva, 4 yrs, treated for SCID.
1999
• Death of Jesse Gelsinger in a gene-therapy experiment
Current Status
Research is still ongoing. Although no gene therapies have been
approved by the FDA for sale, some diseases have been
experimentally successful:
– Melanoma , SCID, Hereditary Blindness, Sickle Cell Anemia

3. How does gene therapy work?
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 therapeutic gene causing cell to return to a normal state

4. Gene Therapy For Cancer
What is cancer?
Cancer, known medically as a malignant neoplasm, is a broad group of various
diseases, all involving unregulated cell growth.
Gene therapy is the latest and a new approach for
cancer treatment.
Chemotherapy for cancer patients often kills healthy
cells as well as cancer cells.
Gene Therapy VS Chemotherapy

5. Gene Therapy For Cancer (contd…)
Strategies
Enhancing the immunogenicity of the tumor.
Enhancing immune cells to increase anti-tumor
activity.
Inserting a "sensitivity" or suicide' gene into the
tumor.
Blocking the expression of oncogenes.
Inserting a wild-type tumor suppressor gene.
Protecting stem cells from the toxic effects of
chemotherapy.
Blocking mechanisms which tumors evade
immunological destruction
Killing tumor cells by inserting toxin genes under the
control of a tumor-specific promoter,

6. Cytokine Genes
Introduction of genes encoding for
proinflammatory cytokines
e.g. IL-12 and IFN-g:
– Induce local inflammation
– Tumor destruction
– Induction of cell mediated immunity
Gene Therapy For Cancer (contd…)
Prominent Strategies
Suicide Genes
HSV-tk
– Phosphorylation of Ganciclovir
– Bystander effect
*HSV-tk: Herpes simplex virus- thymidine kinase

7. Introduction of p53 gene:
– Usually mutated in most
cancers
– Antioncogene
Introduction of MDR-I gene in HSC:
– Increases HSC tolerance to
chemotherapy
– Allows more aggressive treatment
Gene Therapy For Cancer (contd…)
Prominent Strategies (continued)
Tumor Suppressor Genes
Protection of HSC*
*HSC: Hematopoietic Stem Cells

8. Gene Therapy For Cancer (contd…)
Other Strategies
- by inserting toxic genes that encodes diphtheria A chain.
Enhanching immunogenecity
- by introducing genes that encode foreign antigens.
Blocking expression of oncogenes
- by introducing the gene that encodes antisense K-RAS message.
Blocking mechanisms by which tumors evade immunological destruction
- by introducing the gene that encodes antisense IGF-1 message.
Killing tumor cells

9. Gene Therapy For AIDS
Human immuno deficiency virus (HIV) is a lentivirus (a member of the retrovirus
family) that causes acquired immuno deficiency syndrome (AIDS), a condition in
humans in which progressive failure of the immune system allows life-threatening
opportunistic infections and cancers to thrive.
HIV
Contains two strands of (+)
ssRNA.
Contains reverse transcriptase &
integrase.
Integrase helps in the insertion of
HIV DNA into host DNA.
Infects helper T cells and
macrophages.

10. Gene Therapy For AIDS (contd…)
Gene therapy could be used to make immune cells resistant to HIV (the AIDS
virus). It could also be used to help patients destroy HIV and HIV-infected cells by
increasing the body's immune response to these elements.
Intracellular
immunization
Ribozymes
Transdominant
mutant
Trojan horse
Strategies

11. Gene Therapy For AIDS (contd…)
Details about Strategies
Intracellular immunization
An antibody is produced intracellulary by genetic engineering to make the
engineered cells resistant to viral infection.
Ribozymes
These are RNA molecules that contain antisense sequence for specific
recognition and a RNA-cleaing enzymatic activity.
Transdominant mutant
These are proteins that have altered amino acid that render the mutant
protein capable of disrupting the functions of the wild-type protein.
Trojan horse
This is an anti-HIV RNA that contains an HIV-packaging signal coupled to an
anti-HIV nucleic acid.

12. Gene Therapy For Hereditary Diseases
Common Hereditary diseases
A hereditary disease is an illness caused by one or more abnormalities in the genome,
especially a condition that is present from birth (congenital). Most genetic disorders are quite
rare and affect one person in every several thousands or millions.
Single gene inheritance Multifactorial
inheritance
Chromosome
abnormalities
Mitochondrial
inheritance
•Cystic fibrosis,
•Sickle cell anemia,
•Marfan syndrome,
•Huntington's disease
•hemochromatosis.
Heart disease, high
blood pressure,
Alzheimer's disease,
Arthritis
Diabetes
Cancer, and Obesity.
Turner
syndrome
(45,X),
Klinefelter
syndrome (47,
XXY)
Eye disease called
Leber's hereditary
optic atrophy;
a type of epilepsy
called MERRF and
a form of dementia
called MELAS

13. Gene Therapy For Hereditary Diseases (contd…)
SCID affected children are born without an effective immune system. The
therapeutic gene called ADA was introduced into the bone marrow cells of such
patients in the laboratory, followed by transplantation of the genetically corrected
cells back to the same patients.
Severe combined Immune Deficiency
Chronic Granulomatus Disease (CGD)
CGD leads to the patients' inability to fight off bacterial and fungal infections that
can be fatal. Using similar technologies as in the ADA-SCID trial, investigators in
Germany treated two patients with this disease.

14. Gene Therapy For Hereditary Diseases (contd…)
Hemophilia
Patients born with Hemophilia are not able to induce blood clots. The therapeutic
gene was introduced into the liver of patients, who then acquired the ability to have
normal blood clotting time.
Other Genetic Disorders
After many years of laboratory and preclinical research in appropriate animal models
of disease, a number of clinical trials will soon be launched for various genetic
disorders that include congenital blindness, lysosomal storage disease and muscular
dystrophy, among others.
Diabetes
Insulin gene therapy will be considered as including any approach that involves the
introduction of a foreign gene into any cell type in the body, allowing it to produce
insulin.