Mrs. B.Gomathi, Associate Professor and Head, Dept of OBG Nursing, SUM Nursing College, Shiksha 'O' Anusandhan Deemed to be University, Bhubaneswar.

1. GENE THERAPY
Mrs. B.Gomathi,
Associate Professor & Head,
Dept of OBG Nursing, SUM Nursing College
SOA(DTU), BBSR.

2. Introduction
Gene therapy which was first conceived in the
mid-1970s, aims to insert working copies of
genes into cells containing dysfunctional ones.

3. In the 1980s, Scientists began to look into gene
therapy.
They would insert human genes into a bacteria
cell.
Then the bacteria cell would transcribe and
translate the information into a protein.
Then they would introduce the protein into
human cells.

4. Gene therapy was discovered
by Mr. William French
Anderson.
Idea conceptualized in 1972
First Approved Gene Therapy
experiment on human was done
in US in 1990.

5. These trials were stopped when it was
discovered that two of ten patients in one
trial had developed leukemia resulting from
the insertion of the gene-carrying
retrovirus near an oncogene.

6. In 1992 Doctor Claudio Bordignon working at
the Vita-Salute San Raffaele University,
Milan, Italy performed the first procedure of
gene therapy using hematopoietic stem cells as
vectors to deliver genes intended to correct
hereditary diseases.

7. In 1993 Andrew Gobea was born with severe
combined immunodeficiency (SCID).
Blood was removed from Andrew's placenta and
umbilical cord immediately after birth,
containing stem cells.
After four years more treatment was needed.

8. Gene therapy is primarily experimental, with
most human clinical trials only in the research
stages
Cost depends on the trial being performed
and does not involves taking money from the
patients.
More than 5000 patients have been treated
in last 12 years worldwide

9. What is gene therapy?
Gene therapy is the
insertion, alteration, or
removal of genes within an
individual's cells and
biological tissues to treat
disease.
It is a technique for
correcting defective genes
that are responsible for
disease development.

10. Goals of Gene Therapy
Replacing a mutated gene that causes
disease with a healthy copy of the gene.
Inactivating, or “knocking out,” a mutated
gene that is functioning improperly.
Introducing a new gene into the body to
help fight a disease.

11. The most common approach for correcting
faulty genes is to insert a “normal” gene
into the genome to replace an “abnormal”
disease-causing gene.

12. Vector
A vector is a “vehicle” used to deliver genes.
The different types of vectors are:
Retrovirus
Adenovirus
Adeno-Associated Virus
Herpes Simplex Virus
Naked DNA

13. VECTORS
‘Trojan horses’ that sneak the
gene into the cell’

15. Techniques
In vivo technique of
delivering genes to a
patient’s cells.
Ex vivo technique of
delivering genes to a
patient’s cells.

16. METHODS OF VECTOR DELIVERY

17. Challenges in gene therapy
1) Package the gene
2) Protect the gene
3) Targeted delivery to the nucleus and release
in an active form

18. Types of Gene Therapy
There are two types of gene therapy
Germ line
gene therapy
Somatic Gene
therapy

19. Gene therapy targets
Germ line gene therapy
Somatic cell gene therapy
-Gene augmentation
-Gene replacement
-Specific inhibition of gene expression
-Targeted cell death

20. Germ line gene therapy

21. Somatic cell gene therapy
1. Gene augmentation
Simply adding a useful gene into a selected
cell type to compensate for the missing or
flawed version. Useful in treating loss of
function mutations such as Tumour Genes

22. 2. Gene replacement
This strategy replaces the mutant copy with a
correctly functioning copy in situ. Useful for
gain of function mutations such as oncogenes

23. 3. Specific inhibition of gene
expression
Involves silencing of specific genes like activated
oncogenes, by using molecules that degrade RNA
transcripts.

25. 4. Targeted cell death
Tissue specific toxicity as a result of gene therapy.
Useful in cancer therapy
Direct approach

26. Targeted cell death(cont..)
Indirect approach
Stimulating an immune response against selected
cells or eliminating the blood supply.

27. Process

30. Medical Conditions for Which Gene
Therapy Is Being Studied
AIDS
Hemophilia
Liver cancer
Asthma
Lung cancer
Brain tumor
Melanoma
Muscular dystrophy
Breast cancer
Colon cancer
Neurodegenerative
conditions
Diabetes
Ovarian cancer
Heart diseases
Prostate cancer

31. Criteria for a gene therapy
candidate disease
The condition must result from mutations in one
or more genes.
Must know which gene is involved and have an
available DNA copy of that gene.
Must know the biology of the disorder - which
tissue is affected.

32. Adding a normal copy of the gene must fix the
problem.
It must be possible to deliver the gene to cells
of the affected tissue.

33. Benefits
Cures could be developed for hereditary
diseases such as Huntington’s Disease and
various cancers.
All future generations could be saved from
developing terrible life -threatening diseases.

34. Limitations of Gene Therapy
Short-lived nature of gene therapy
Immune response
Problems with viral vectors (toxicity, immune and
inflammatory responses)
Multigene disorders
Chance of inducing a tumor ( insertional
mutagenesis)
Only partially effective and must be administered
continuously

35. The First Case
The first gene therapy was performed on
September 14th, 1990
Ashanti DeSilva was treated for SCID
Sever combined immunodeficiency

36. Doctors removed her white blood cells,
inserted the missing gene into the WBC,
and then put them back into her blood
stream.
This strengthened her immune system
Only worked for a few months

37. The first death associated with gene therapy
occurred on September 18, 1999, at the
University of Pennsylvania. Jesse Gelsinger
was participating in a clinical trial.
Gelsinger, who was 18 years old at the time
of the treatment, had a deficiency of
ornithine transcarboamylase, an important
enzyme in the metabolism of ammonia.

38. The gene therapy Gelsinger took triggered a
chain reaction in his immune system, resulting in
hepatic and respiratory failure, and
consequently, his death four days after being
treated.

39. Other Examples of Gene Therapy
Cystic fibrosis
Adenovirus selected (non-integrating respiratory
virus)
Gene therapy trials – 3 Research teams, 10
patients/team
2 teams administered virus via aerosol delivery
into nasal passages and lungs
1 team administered virus via nasal passages only
Successful results obtained

40. Familial Hypercholesterolemia
Defective cholesterol receptors on liver
cells
Fail to filter cholesterol from blood
properly
Cholesterol levels are elevated, increasing
risk of heart attacks and strokes
1993 First attempt
Retroviral vector used to infect liver cells
ex vivo
Infused back into patient
Improvement seen
Has been used in many trials since then

41. Current status
Food and Drug Administration (FDA) has not
yet approved any human gene therapy product
for sale.

42. Hospitals in India
Medanta (the medicity), Haryana.
Max health care
Fortis health care, Delhi
Apollo hospital, Delhi
Seven Hills hospital, Mumbai
Wellness destination, Sultanpur, Uttar
Pradesh
Sir Ganga ram, New Delhi

43. Abdur Razzaaque Ansari memorial hospital, ARAM,
Jharkhand, Ranchi
Acupuncture India centre, Delhi
Jehangir hospital, Pune
Rajiv Gandhi cancer institute and research centre, Delhi
Royal Medical tour Pvt. Ltd, Mumbai
Tata memorial hospital mumbai
The meditour, Ahemdabad
The Nova medical centre, Delhi.

44. THANK YOU