Discussing what gene therapy is, its types and methods used.

1. ALEENA HAQQI
KHUSHBAKHT KHAN
KAFILA KOUSAR
HANIA SHAH
FAIZA NASEER
SUMAIYA LIAQUAT
COURSE : PRINCIPLES OF MOLECULAR BIOLOGY

2.  Introduction To Gene Therapy
 Gene Therapy Types
 Steps Involved In Gene Therapy
 Applications
 Current Status
 Limitations
 Future Perspective

3. INTRODUCTION TO GENE THERAPY
By Sumaiya Liaquat

4. Correction of
Abnormal Gene
Therapeutic
delivery of nucleic
acid into a patient's
cells

7. TYPES OF
TECHNIQUES
Gene
Augmentation
Therapy
Gene Inhibition
Therapy

9. Somatic Cell Gene
Therapy
Bone Marrow
Cells, Blood Cells,
Skin Cells, Etc.
Non-heritable
Germline Gene
Therapy
Sperms And Eggs
Heritable

10. EX Vivo
Modifies Cells Outside The
Body Followed By
Transplantation
Target Bone Marrow Stem
Cells, Liver Cells, Blood
Vessel Smooth Muscle
Cells And TIL
IN Vivo
Direct Introduction Of The
Genetic Materials Into The
Human Body.
For The Cells whose
cultures cannot produce
enough cells

13. STEPS INVOLVED IN GENE THERAPY
By ALEENA HAQQI

15. Specific
Efficient
Delivery
Non-
Immunogenic
Non-
Inflammatory
Safe for patient
&
Enviroment
Long term
Expression

16. Types of Vector
Viral
Adenovirus
AVV
Retrovirus
Lentivirus
HSV
Non-Viral
(Plasmid)
Physical
MEthod
Electroporation
Gene Gun
Microinjection
Chemical
Method
Calcium
Chloride
Liposomes

17. Higher
Transgene
Capacity
Important
Sequence
required to
Insert DNA
Promoter
Sequence
Inverted
Terminal Repeat
Control
Elements
Antibiotic
Resistant
Gene
Genes Essential
for Viral
Enzymes

21. APPLICATIONS OF GENE THERAPY
By Kafila Kousar

22. Replace Missing or defective
gene
Deliver Gene That speed the
destructio of cancer cells or
revert them back to normal
Deliver Viral or Bacterial gene
as a form of vaccination
Deliver Gene that stimulate the
healing of a wound
Deliver Gene to treat genetic
disorders
Provide genes that promote or
impede the growth of new
tissue

23. The method can be used for the
diagnosis of disease if approved
globally.
It is used in the diagnosis of inherited
diseases such as cystic fibrosis,
Duchenne muscular dystrophy,
muscular atrophy and haemophilia.
Furthermore, efforts are being made
to develop gene therapy against
monogenic disorders such as
thalassemia and sickle cell anaemia.
The in vivo gene therapy or viral vector-
mediated gene therapy is a good option
for treating diseases like Parkinson’s
disease, Alzheimer’s disease and brain
tumours.

24. Teeth and bone repair and
regeneration
DNA vaccines
insulin and thrombotic factors.
Cancer Treatment

25. Cardiac Disorders
Neurological Disorders
Infectious Disorders
Autoimmune Disorders
Retinal Degeneration
Designer Babies

26. CURRENT STATUS OF GENE THERAPY
By Khushbakht Khan

27. 1990
First successful gene therapy trial on 4 years old girl “Ashanti Desilva”.
Severe combined immune deficiency.
1992
First procedure of gene therapy using hematopoietic stem cells as vectors to correct
hereditary disease.
2003
Los Angeles research team used liposome coated in a polymer to insert genes into brain.
Parkinson’s disease.
2005
Successfully treated metastatic melanoma in two patients using killer T cells genetically
retargeted to attack the cancer cells
2007
Leber’s Congenital amaurosis
Sub-retinal delivery of recombinant AAV carrying RPE65 gene
2010
Achromatopsia in dogs
Ideal model to develop gene therapy directed to cone photoreceptors
2013
heart disease
Increase the level of SERCA2a protein in the heart muscles to improve their function
2014
University of Pennsylvania researchers
Treated 12 HIV patients

28. GENE THERAPY
CLINICAL TRIALS
WORLDWIDE
Number of
trials per year
Countries
Phases of
development
Vectors used
for gene
delivery
Trials status
Diseases
targeted by
gene
therapies
1990 – 2015 : 2335
2018: 2731
Monogenic diseases
Cancer 64.41%
Pharmaceutical Research and
Manufacturers of America
(PhRMA)
771 new oncology drugs and
vaccines currently in clinical trials
or submitted to FDA for review in
US companies.

29. DISTRIBUTION OF GENE THERAPY CLINICAL TRIALS BY COUNTRY

30. PHASE OF DEVELOPMENT OF GENE THERAPY CLINICAL TRIALS
Among which,
30% are cancer
therapies.

31. Only causes a mild immune response.
Infects both dividing and non-dividing cells.
Remains in an extra-chromosomal state.

32. European Medicine
Agency
US Food and Drug
Administratio n (FDA)
National Institute of
Health (NIH)
Recombinant DNA
Advisory Committee
(RAC)
Help medicine developers
prepare marketing authorization
applications for human
medicines.
Safety and control
measures associated
with gene therapy.
•Reviews gene therapy
protocols
•Financial Support
General Cost
$375,000 and $875,000

33. Disease Drug Company
β-thalassemia Zynteglo Bluebird Bio
Spinal muscular atrophy Zolgensma Novartis
RPE65 deficiency
Luxturna
Spark
Head and neck squamous cell
carcinoma
Gendicine
Shenzhen SiBionoGeneTech

34. LIMITATIONS GENE THERAPY
By Faiza Naseer

35. Funds/
Resources
Ethical
barriers
Public
acceptanc
e
Religious
values

36. Lack of resources
• Short lived nature (rapid dividing of cells)
• Immune response is potential risk
• Disorders by defects in multiple genes (multigene
disorders)
• Virus as vectors effects host
Funds
• Required improvements in global regulatory bodies and
their systems
• Collaboration in acknowledging that cell and gene
therapy
• Innovation in R&D needs incentives

37. Ethical Barriers
• Who will have access to therapy
• Is it interfering God’s plan
• Is it alright to use gene therapy in prenatal stage of
development of babies?
Public Acceptance
• High Cost (need insurance) / Good and bad distinguished
• which traits are normal and which constitute disability or
disorder?
• enhance basic human traits such as height intelligence or
athletic ability
• Cosmetic industry may monopolized this gene

38. Religious Values
No Comments

39. FUTURE PERSPECTIVE OF GENE THERAPY
By Hania Shah

40. • Gene therapy has the potential to change;
The conventional symptomatic approach to disease treatment
Provide options for diseases that cannot be treated in any other way.
• So in future it is expected to treat
Monogenic
diseases like
haemophilia
Cardiovascular
diseases
Many types of
difficult to treat
and chemo-
resistant
Cancers
Incurable
conditions such
as Alzheimer’s
disease and
Parkinson’s
disease

41. Disease- Gene of interest Company perusing gene
therapy
AADC deficiency (CNS) AADC PTC Therapeutics
Cystic Fibrosis CTFR Vertex
Congestive heart failure Adenyl cyclase 6 Renova
Choroideremia CHM Spark
Metachromatic
leukodystrophy
ARSA GlaxoSmithKline (GSK)
• Table of gene therapies to be persuaded in 2020

42. • The hepothetical non-therapeutic use of genes, genetic elements
or cells that have the capacity to enhance athletic performance"
• There are numerous genes of interest as agents for gene doping;
Erthropiotin
Insulin like growth factor 1
Myostatin
Endorphin
Alpha-actinine-3
Present in skeletal
muscles, different forms,
related to power

43. Improving viral vectors (AAV and lentivirus), integrate their genome
into the chromosomes of nondividing cells (e.g., brain, peripheral
nerves).
Lentiviral vector-mediated transgene expression can also be
maintained for long periods of time.
Scientists are working on defective HIV genome in which lentiviral
vector will be used

44. Cost effectiveness
A treatment that
is unavailable
to patients who
need it has no
value at all.
Patient
access to gene
therapy may be
hampered by
payer challenges
to covering the
upfront costs
of gene therapies

45. • When optimizing the efficacy of a new drug, a central challenge is the
search for minimum effective dose.
• As companies move through Phase 1 and 2 trials, they tinker with viral
load, in order to optimize exogenous protein levels in patients. As you
increase the intensity of the gene therapy (viral load), you should be
inserting more genetic material for the deficient protein into the necessary
cells.
• However, an excessively high viral load can cause toxicity issues (liver
damage, hyper-activated immune system).
• So, an ideal gene therapy protocol will administer the minimum effective
dose of virus.

46. • The introduction and implementation of gene therapy has opened new
doors in the field of Health sciences.
• But implementing a safe and effective gene therapy has not been so easy
due to high cost, finessing appropriate viral system, immune rejection and
ethical issues.
• Safety is always a concern when live vector systems are used for human
gene therapy the ideal expression vector for use in humans has yet to be
identified.
• For patients to get assess to these treatments, cost effectiveness should
be included in the futuristic therapies

47. Bender, E. (2018). Regulating the gene-therapy revolution. Nature, 564, S20-
S22.
Hasan, N., & Saini, S. (2014). Gene therapy: Current status and future
perspectives. therapy, 3, 4.
Misra, S. (2013). Human gene therapy: a brief overview of the genetic
revolution. J Assoc Physicians India, 61(2), 127-133.
http://geneticeducation.co.in/gene-therapy-types-vectors-viral-and-non-viral-
process-applications-and-limitations/
https://www.risingtidebio.com/what-is-gene-therapy-uses/#recent