This document summarizes the history and development of gene therapy from the 1950s to the present. It discusses key events like the isolation of genes in the 1970s and 1980s and the first human gene therapy treatment in 1990. It outlines various gene therapy strategies like ex vivo and in vivo approaches and delivery methods like viruses, liposomes, microinjection, and electroporation. Challenges of gene therapy are also summarized like ethical issues, high costs, and ensuring safety. The document aims to provide an overview of the progress of gene therapy and remaining barriers to its clinical application and acceptance.

1. Is there a permanent solution for them?
cystic fibrosis
hemophilias
Colour blindness
Leukemias
Thalessemiaas
HIV
Parkinsons disease ……….
Dr Santosh KM
Narayana Health
Department of internal medicine

2. GENE THERAPY

3. HISTORY AND DEVELOPMENT
OF GENE THERAPY
• characteristics traits of parents
• scientific study of genetics began in 1850s,

4. 1950s
American biochemist James Watson
and
British biophysicist Francis Crick
"We used to think that our fate was in our stars, but now we know that, in
large measure, our fate is in our genes, "quotes James Watson

5. • early 1970s enzymes - DNA cut and glue
• The isolation of genes
• Genetic engineering in 1980s
• 1989 - Dr. Steven Rosenberg to test the safety and effectiveness of the
gene therapy process in cancer patients

6. • A four-year old girl became the first gene therapy patient on September
14, 1990 at the NIH Clinical Center. She has adenosine deaminase (ADA)
deficiency,
• White blood cells underwent ex vivo process
• The corrected cells were re-injected into her.
• Dr. W. French Anderson helped develop this landmark clinical trial

7. • 1992: Dr Claudio Bordignon performed the first procedure of gene
therapy using hematopoietic stem cells as vectors to deliver genes
intended to correct hereditary diseases
• 2006-07: Scientists at the NIH(Bethesda, Maryland) have successfully
treated metastatic melanoma in two patients. This study constitutes one
of the first demonstrations that gene therapy can be effective in treating
cancer.[1]
• 2007- 2015: Research is still ongoing and the number of diseases that has
been treated successfully by gene therapy increases.
Retinal disease
cystic fibrosis
hemophilias
Colour blindness
Leukemias
Thalessemiaas
Parkinsons disease
1 Morgan, R. A.et al (2006)."Cancer Regression in Patients After Transfer of
Genetically Engineered Lymphocyte". Science 314(5796): 126–
129. Bibcode:2006Sci...314..126M.doi:10.1126/science.1129003. PMC 2267026.PMID
16946036.

8. • 2011: Medical community accepted that it can cure HIV as in
2008, Gero Hutter has cured a man from HIV using BMT
• The scope for future interest in search for cure began
• Current status of gene therapy – phase 1-111 trails
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570487/
http://learn.genetics.utah.edu/content/genetherapy/gtsuccess/

9. Human Genome Project
• the international, collaborative research program whose goal was the complete mapping and
understanding of all the genes of human beings.
• 1990 to April 2003
• about 20,500 human genes
• From molecular medicine to human evolution.
• Sequencing of the DNA, helped in genotyping of specific viruses to direct appropriate
treatment;
• Identification of mutations linked to different forms of cancer.
• The design of medication and more accurate prediction of their effects; advancement
in forensic applied sciences; biofuels and other energy applications; agriculture, animal
husbandry, bioprocessing; risk assessment; bioarcheology, anthropology and evolution.

10. Proportion of protocol for human gene therapy trails related to various diseases
Morgan RA, Blaese RM. Gene therapy: Lessons learnt from the past decade. BMJ 1999:319:1310.
Revised in 2012

12. Types of mutations

13. Missense mutation

14. Beta thalassaemia (β-globin)
Duchenne muscular dystrophy (dystrophin)
Cystic fibrosis (caused by the G542X mutation in the cystic fibrosis
transmembrane conductance regulator gene).

15. CROHN disease - In 2001, Ogura et al. found a frameshift mutation in NOD2 (chromosome 16) that led
to a cytosine insertion that ultimately reduced the protein's activity
Hypertrophic Cardiomyopathy
Mutations in the Troponin C gene (TNNC1)

16. Classification
• Germ line gene therapy
• Somatic gene therapy

17. Somatic cell gene therapy
Most commonly used
 Bone marrow cells
 Neural cells
 hepatocytes

18. Germ line gene therapy
Sperm or egg
Result in permanent changes
eliminating some diseases from
a particular family.
Ethically-"playing God”

19. Patient with HBV/HCV infection - embryonic stem cell or induced pleuripotent stem cell

20. Strategies
• Ex vivo
• In vivo

24. Liposome
• a spherical vesicle having at least one lipid bilayer

25. Liposome mediated gene transfer
1. Simplicity.
2. Long term stability.
3. Low toxicity.
4. Protection of nucleic acid from degradation
Less immunogenecity

26. NAKED DNA
• is Histone-free DNA passed from cell to cell during a gene transfer process
• Application – DNA vaccines and gene transfer
• IV/IM
Transformation - taken up by the recipient cell which will
give the recipient cell a new characteristic or phenotype
Transfection - infecting a cell with a foreign gene
•Malaria
•Hepatitis
•TB
•HIV

27. microinjection
Inverted microscope magnification power of around 200x

28. Gene gun
• DNA (or RNA) “sticky,” adhering to biologically inert particles
such as metal atoms (usually tungsten or gold).
• Shoot the gun
• Taking up or DNA/RNA
• Identifying the cell and culture

29. Electroporation
• Electroporation uses electrical pulse to produce transient
pores in the plasma membrane thereby allowing DNA into the
cells.
• These pores are known as electropores
• The cells are placed in a solution containing DNA and
subjected to electrical pulse to cause holes in the membrane.
• The foreign DNA fragments enter through holes into the
cytoplasm and then to nucleus

30. 1. Method is fast.
2. Less costly.
3. Applied for a number of cell types.
4. Simultaneously a large number of cell
can be treated.
5. High percentage of stable
transformants can be produced

32. Viral vectors

36. Barriers of gene therapy

37. • Give a chance of a normal life to baby born with genetic
disease.
• Give hope of healthy life to cancer patient.
• For certain disease that do not have any cure except gene
therapy, it could save many lives
ADVANTAGES OF GENE THERAPY

38. • The genetic testing, screening and research in finding the availability of
certain gene is very controversy.
• May increase rate of abortion if prenatal test regarding baby with genetic
disease is done.
• The cost is very high and the patient might need an insurance to cover the
treatment.
• Cosmetic industry may monopolized this gene therapy if it is used in
enhancing beauty and in vanishing the aging effect, rather than used for
treatment of a disease
DISADVANTAGES OF GENE
THERAPY

39. Questions that raise
• How can “good” and “bad” uses of gene therapy be distinguished?
• Who decides which traits are normal and which constitute a disability or
disorder?
• Will the high costs of gene therapy make it available only to the wealthy?
• Could the widespread use of gene therapy make society less accepting of
people who are different?
• Should people be allowed to use gene therapy to enhance basic human
traits such as height, intelligence, or athletic ability?

41. Thank you all for your patient listening