Spreading Knowledge is a great Legacy. MMG

1. GENE THERAPY
Correcting defective genes

2. GENE THERAPY
Any procedure intended to treat or
alleviate disease by genetically
modifying the cells of a patient

3. Heard at the Genetics Clinic:
• “Can you take out the bad gene?”
• “Can you fix that gene?”
• “Can you remove the extra chromosome?”
• “By the time my daughter gets the disease, will
be there be gene therapy to treat it, or at least to
her babies”
• “Are doctors working on gene therapy for this?”

4. History
• 1960’s : The concept of Gene Therapy was
introduced.
• 1972 : Friedman and Roblin authored a paper in
Science titled "Gene therapy for human genetic
disease.”
• 1984: A retrovirus vector system was designed
that could efficiently insert foreign genes into
mammalian chromosomes.

5. History
• 1990: The first approved gene therapy in the
US took place on 14 September 1990, at the
National Institutes of Health (NIH), under the
direction of William French Anderson.
• Four-year-old Ashanti DeSilva received
treatment for a genetic defect that left her with
ADA-SCID, a severe immune system
deficiency.

6. History
• 1992: Doctor Claudio Bordignon performed the
first procedure of gene therapy using
hematopoietic stem cells as vectors to deliver
genes intended to correct hereditary diseases.
• 1999: Death of Jesse Gelsinger in a gene-therapy
experiment

7. History
• 2003 : a research team inserted genes into the
brain for the first time. They used liposomes
which, unlike viral vectors, are small enough to
cross the blood–brain barrier.
• 2006 : successful use of gene therapy to treat two
adult patients for X-linked chronic granulomatous
disease.
• 2007: first gene therapy trial for inherited retinal
disease

8. History
• 2010 : an 18 year old male patient in France with
beta-thalassemia major had been successfully
treated.
• 2011: Medical community accepted that it can
cure HIV as in 2008, Gero Hutter has cured a
man from HIV using gene therapy.
• 20011- 2019: Research is still ongoing and the
number of diseases that has been treated
successfully by gene therapy increases.

10. GENE THERAPY
 Delivery mechanism
– Ex vivo
– In vivo
– In situ
 Type of cells modified
– Germ-line cells
– Somatic cells
 Mechanism of modification
– Gene augmentation/supplementation
– Gene replacement
– Targeted inhibition of gene expression
– Targeted killing of specific cells

12.  Germ-line gene therapy
– Modification of gametes, zygote or early embryo
– Permanent and transmissible
– Banned due to ethical issues
 Somatic cell gene therapy
– Modification of somatic cells, tissues etc
– Confined to the patient
TYPES OF CELLS MODIFIED

13. • Targeted at disorders where pathogenesis is
reversible
• Recessive disorders are more amendable to
treatment than dominant disorders
• Gain-of-function mutations are untreatable
by GAT
Mechanism of modification
1. Gene augmentation

14. Mechanism of modification
2. Gene replacement

15. Mechanism of modification
3. Targeted killing of specific cells

16. Mechanism of modification
4.Targeted inhibition of gene
expression
Gain-of-function diseases where mutant
gene is producing a harmful protein

17. Amenability to gene therapy
 Mode of inheritance
 Identity of molecular defect
 Nature of mutation product
 Accessibility of target cells and
amenability to cell culture
 Size of coding DNA
 Control of gene expression

18. Gene transfer
Cloned
gene
Integrated
gene
Episomal
gene
Cell division

19.  Adverse response to the vector
 Insertional mutatgenesis resulting in
malignant neoplasia
 Insertional inactivation of an essential gene
 Viruses may infect surrounding health tissues
 Overexpression of the inserted gene may lead
to so much protein that it may become
harmful
Risks associated with
gene therapy

20. SUCCESS CASES OF GENE THERAPY

21. GENE THERAPY CURES
BLINDNESS
• Cure blindness of inherited condition
• Leber’s congenital amaurosis - inherited disease
caused by an abnormality in a gene called
RPE65.
• The condition appears at birth or in the first few
months of life and causes progressive worse and
loss of vision.

22. GENE THERAPY REDUCES PARKINSON’S
DISEASE SYMPTOMS
• It has significantly improved the weakness of the
symptoms such as tremors, motor skill problems,
and rigidity
• Done with local anesthesia, used a harmless,
inactive virus [AAV-2 ]

23. ADVANTAGES
• Gene therapy has the potential to eliminate
• and prevent hereditary diseases such as cystic
fibrosis, ADA- SCID etc.
• It is a possible cure for heart disease, AIDS and
cancer.
• It gives someone born with a genetic disease a
chance to life.
• It can be used to eradicate diseases from the
future generations.

24. DISADVATAGES
• Long lasting therapy is not achieved by gene
therapy; Due to rapid
• dividing of cells benefits of gene therapy is
short lived.
• Immune response to the transferred gene
stimulates a potential risk to gene therapy.

25. • Disorders caused by defects in multiple genes
cannot be treated effectively using gene
therapy.
• Viruses used as vectors for gene transfer may
cause toxicity, immune responses, and
inflammatory reactions in the host.

26. ELEMENTS OF GENE THERAPY