Gene TherapyGene Therapy

By

Mostafa A. Askar

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 ProblemsInherited Diseases Treated by Gene Therapy; Trails

Types of Gene Therapy

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 ProblemsInherited Diseases Treated by Gene Therapy; Trails

Types of 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.

Definition of Gene Therapy

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 ProblemsInherited Diseases Treated by Gene Therapy; Trails

Types of Gene Therapy

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.

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 ProblemsInherited Diseases Treated by Gene Therapy; Trails

Types of Gene Therapy

Somatic gene therapy

In Utero gene therapy Germ line gene therapy

Types of gene therapy

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

In In UteroUtero gene therapy gene therapy

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

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

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 ProblemsInherited Diseases Treated by Gene Therapy; Trails

Types of Gene Therapy

General principles of Gene therapy

Identification and characterization of gene Cloning of gene Choice of vector Method of delivery Expression of gene

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

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 ProblemsInherited Diseases Treated by Gene Therapy; Trails

Types of Gene Therapy

Viral vectors.

Non-viral delivery.

DNA delivery is mainly accomplished by either:

Vectors

Adeno viruse sAdeno viruse s

Adeno Asso ciate d viruse sAdeno Asso ciate d viruse s

Re to viruse sRe to viruse s

He rpe s Simple x viruse sHe rpe s Simple x viruse s

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

AdenovirusesAdenoviruses

Adenovirus vector in Gene Therapy

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 injections

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

Retroviruses

* Infect * Infect ONLYONLY dividing cells dividing cells* Integration is random, causing* Integration is random, causing “ “ Inse rtio nal Mutg e ne sisInse rtio nal Mutg e ne sis ” .” .

Retroviruses

Disadvantages

* Their ability to integrate in host DNA.

Advantages

Non-viral delivery in gene therapy

Particle bombardment

Receptor-mediated uptake

Liposomes

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

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

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

Liposomes

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 ProblemsInherited Diseases Treated by Gene Therapy; Trails

Types of Gene Therapy

Antisense Gene Therapy

Gene Therapy to Induce Apoptosis

Anti-Angiogenic Gene Therapy

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 ProblemsInherited Diseases Treated by Gene Therapy; Trails

Types of Gene Therapy

1.1. Short Lived Short Lived

2. Immune Response2. Immune Response

3. Viral Vectors3. Viral Vectors– may cause disease once insidemay cause disease once inside

Problems with Gene Problems with Gene TherapyTherapy

4. Multigene Disorders4. Multigene Disorders– Heart disease, high blood pressure, Heart disease, high blood pressure,

Alzheimer’s, arthritis and diabetes Alzheimer’s, arthritis and diabetes are hard to treat because you need to are hard to treat because you need to introduce more than one geneintroduce more than one gene

5. May induce a tumor if integrated in 5. May induce a tumor if integrated in a tumor suppressor gene because a tumor suppressor gene because insertional mutagenesisinsertional mutagenesis

Problems with Gene Problems with Gene TherapyTherapy

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 ProblemsInherited Diseases Treated by Gene Therapy; Trails

Types of Gene Therapy

Gene Therapy trials for inherited diseases

Lung

• Cystic Fibrosis (CF).

Diseases Treated by Gene Therapy

Bone Marrow Adenosene Deaminase Deficency(ADA)

Brain (Alzheimer’s disease)

Liver (Factor VIII deficiency.)

Questions?Questions?