This document provides an overview of gene therapy, including definitions, aims, delivery methods, approaches, problems, and applications. Gene therapy involves inserting, altering or removing genes in a patient's cells to treat disease. It aims to correct defective genes. Delivery is mainly through viral vectors like adenoviruses or retroviruses, or non-viral methods like particle bombardment or liposomes. Gene therapy approaches include antisense therapy, inducing apoptosis, or anti-angiogenesis. Problems include short-lived effects, immune responses, vector safety, and challenges of multigene disorders. Diseases being investigated include cystic fibrosis, ADA deficiency, Alzheimer's, hemophilia and others.

2. Gene TherapyGene Therapy
By
Mostafa A. Askar

3. Definition of Gene Therapy
Aim of Gene Therapy
DNA delivery in Gene Therapy; How & With What
General Principles of Gene Therapy
Gene Therapy Approach
Gene Therapy Problems
Inherited Diseases Treated by Gene Therapy; Trails
Types of Gene Therapy

4. Definition of Gene Therapy
Aim of Gene Therapy
DNA delivery in Gene Therapy; How & With What
General Principles of Gene Therapy
Gene Therapy Approach
Gene Therapy Problems
Inherited Diseases Treated by Gene Therapy; Trails
Types of Gene Therapy

5. 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.
Definition of Gene Therapy

6. Definition of Gene Therapy
Aim of Gene Therapy
DNA delivery in Gene Therapy; How & With What
General Principles of Gene Therapy
Gene Therapy Approach
Gene Therapy Problems
Inherited Diseases Treated by Gene Therapy; Trails
Types of Gene Therapy

7. Aim of Gene Therapy
The most common form of gene therapy
involves the insertion of functional genes into
an unspecified genomic location in order to
replace a mutated gene, but other forms
involve directly correcting the mutation or
modifying normal gene that
enables a viral infection.

8. Definition of Gene Therapy
Aim of Gene Therapy
DNA delivery in Gene Therapy; How & With What
General Principles of Gene Therapy
Gene Therapy Approach
Gene Therapy Problems
Inherited Diseases Treated by Gene Therapy; Trails
Types of Gene Therapy

9.  Somatic gene therapy
 In Utero gene therapy
 Germ line gene therapy
Types of gene therapy

10. In the case of somatic gene therapy, the
therapeutic genes are transferred into
the somatic cells of a patient. Any
modifications and effects will be
restricted to the individual patient only,
and will not be inherited by the patient's
offspring or later generations.
Somatic gene therapy

11. InIn UteroUtero gene therapygene therapy
It involves gene therapy of fetuses
whilst in the womb. There is some
concern that the germline
will be affected.

12. In this case; Germ cells (Ex. sperm or
eggs) are modified by the introduction
of functional genes, which are
integrated into their genomes.
Therefore, the change due to therapy
would be heritable and would be passed
on to later generations.
Germ line gene therapy

13. Definition of Gene Therapy
Aim of Gene Therapy
DNA delivery in Gene Therapy; How & With What
General Principles of Gene Therapy
Gene Therapy Approach
Gene Therapy Problems
Inherited Diseases Treated by Gene Therapy; Trails
Types of Gene Therapy

14. General principles of Gene
therapy
Identification and characterization of gene
Cloning of gene
Choice of vector
Method of delivery
Expression of gene

15.  Non-pathogeneic.
 Capable of integrating DNA into host
genome at a single site.
 Able to carry large amounts of DNA.
 Unable to cause immune response.
 Target cells specifically.
Characteristics of the ideal vector

16. Definition of Gene Therapy
Aim of Gene Therapy
DNA delivery in Gene Therapy; How & With What
General Principles of Gene Therapy
Gene Therapy Approach
Gene Therapy Problems
Inherited Diseases Treated by Gene Therapy; Trails
Types of Gene Therapy

17.  Viral vectors.
 Non-viral delivery.
DNA delivery is mainly
accomplished by either:

18. Vectors
Adeno virusesAdeno viruses
Adeno Asso ciated virusesAdeno Asso ciated viruses
Reto virusesReto viruses
Herpes Simplex virusesHerpes Simplex viruses

19. * dsDNA Viruses.* dsDNA Viruses.
* Non-integrating viruses.* Non-integrating viruses.
* Infect dividing & non-dividing* Infect dividing & non-dividing
cells.cells.
AdenovirusesAdenoviruses

20. Adenovirus vector in Gene Therapy

21. Adenoviruses AdvantagesAdenoviruses Advantages
* Non-oncogenic.* Non-oncogenic.
* Relatively easy to culture.* Relatively easy to culture.
* Proteins functions are known.* Proteins functions are known.
* Complete DNA sequence is* Complete DNA sequence is
available.available.
Adenoviruses Disadvantages
Transient expression leads to
multiple

22. * RNA Viruses.* RNA Viruses.
* Incorporating Viruses.* Incorporating Viruses.
* Infect dividing cells.* Infect dividing cells.
Retroviruses

23. * Infect* Infect ONLYONLY dividing cellsdividing cells
* Integration israndom, causing* Integration israndom, causing
““ Insertio nalMutgenesisInsertio nalMutgenesis”.”.
Retroviruses
Disadvantages
* Their ability to integratein host DNA.
Advantages

24. Non-viral delivery in
gene therapy
Particle bombardment
Receptor-mediated uptake
Liposomes

25. Particle bombardment. DNA is fired through
the cell walls and membranes on metal
particles. This method was originally
developed to get DNA into plants. However, it
has also been used to make transgenic animals
and is occasionally used for humans.
Particle bombardment

26. Receptor-mediated uptake. DNA
is attached to a protein that is
recognized by a cell surface
receptor. When the protein enters
the cell, the DNA is taken in with
it.
Receptor-mediated uptake

27. Liposomes are spherical vesicles
composed of phospholipid. They
have been used in around 10% of
gene therapy trials.
Liposomes

28. Definition of Gene Therapy
Aim of Gene Therapy
DNA delivery in Gene Therapy; How & With What
General Principles of Gene Therapy
Gene Therapy Approach
Gene Therapy Problems
Inherited Diseases Treated by Gene Therapy; Trails
Types of Gene Therapy

29. Antisense Gene Therapy

30. Gene Therapy to Induce Apoptosis

31. Anti-Angiogenic Gene Therapy

32. Definition of Gene Therapy
Aim of Gene Therapy
DNA delivery in Gene Therapy; How & With What
General Principles of Gene Therapy
Gene Therapy Approach
Gene Therapy Problems
Inherited Diseases Treated by Gene Therapy; Trails
Types of Gene Therapy

33. 1.1. Short LivedShort Lived
2. Immune Response2. Immune Response
3. Viral Vectors3. Viral Vectors
– may cause disease once insidemay cause disease once inside
Problems with GeneProblems with Gene
TherapyTherapy

34. 4. Multigene Disorders4. Multigene Disorders
– Heart disease, high blood pressure,Heart disease, high blood pressure,
Alzheimer’s, arthritis and diabetesAlzheimer’s, arthritis and diabetes
are hard to treat because you need toare hard to treat because you need to
introduce more than one geneintroduce more than one gene
5. May induce a tumor if integrated in5. May induce a tumor if integrated in
a tumor suppressor gene becausea tumor suppressor gene because
insertional mutagenesisinsertional mutagenesis
Problems with GeneProblems with Gene
TherapyTherapy

35. Definition of Gene Therapy
Aim of Gene Therapy
DNA delivery in Gene Therapy; How & With What
General Principles of Gene Therapy
Gene Therapy Approach
Gene Therapy Problems
Inherited Diseases Treated by Gene Therapy; Trails
Types of Gene Therapy

36. Gene Therapy trials for
inherited diseases
Lung
• Cystic Fibrosis
(CF).

37. Diseases Treated by Gene
Therapy
Bone Marrow Adenosene
DeaminaseDeficency(ADA)
Brain (Alzheimer’sdisease)
Liver(Factor VIII deficiency.)

38. Questions?Questions?