Gene TherapyPrepared by: 3rd year medicine students in

King AbdulAziz University.

Objectives

● 1-Definition of gene therapy.

● 2-Mechanism of gene therapy.

● 3-Types of gene therapy.

● 4-Types of somatic gene therapy.

● 5-Some case study of gene therapy.

● 6-Ethical issues surrounding gene therapy.

• Definition: an experimental technique for correcting defective genes that are responsible for diseases development.

What is gene therapy?

• Gene therapy is currently available in research settings.

• The most common form of gene therapy involves inserting a normal gene to replace an abnormal gene

• Other approaches used:▪ 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.

What is gene therapy?

Severe combined immune-deficiencies (SCID)

Hemophilia

Cancer

Parkinson's disease

HIV

and other diseases...

Gene therapy holds promise for treating a wide range of diseases, including:

Objective 2

MECHANISM OF GENE THERAPY

• A gene can't easily be inserted directly into the cells. Rather, it usually has to be delivered using a carrier, called a vector.

Mechanism of Gene Therapy

• The vector is genetically engineered to deliver the gene into cells.

• Certain viruses are often used as vectors because they can deliver the new gene by infecting the cell.

Retroviruses, they integrate their genetic material (including the new gene) into a chromosome in the human cell.Like: HIV1 & SIV

Adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome.

Examples for Viral Vectors

9

Gene therapy using retrovirus vector

10

Gene therapy using adenovirus vector

TYPES OF GENE THERAPY

Objective 3

Types of Gene Therapy

• It is prohibited for ethical reasons.

• Result in permanent changes.

• Possibility of eliminating some diseases from a particular family.

• Also raises controversy:

Some people view this type of therapy as unnatural.

Others have concerns about the technical aspects.

Germ Line Gene Therapy

• In germ line gene therapy, the therapeutic DNA is delivered to a germ cell. As germ cells are needed to reproduce sexually, any changes to a germ cell will be passed on to future generations

Germ Line Gene Therapy

TransgeniccellNew gene Blastocyst

stage

New trait

Somatic Gene Therapy

• Transporting the gene to the target cells or tissue is also problematic.

• Appropriate and acceptable for many disorders, including cystic fibrosis, muscular dystrophy, cancer, and certain infectious diseases.

• Any modification to a somatic cell will not affect the next generation (an offspring). In somatic gene therapy, the therapeutic DNA is transferred to the somatic cells of a patient.

Somatic Gene Therapy

Altering the genes

New trait

Objective 4

TYPES OF SOMATIC GENE THERAPY

18

Types of Somatic Gene Therapy

Objective 5

SOME CASE STUDY OF GENE THERAPY

1-Case of Gene Therapy went successfully

Ashanti DeSilvaThe first successful case of Gene Therapy on a young girl named Ashanti DeSilva.

What was the problem?

• Adenosine deaminase deficiency• This disease is caused by a mutation in ADA gene.

• What is Adenosine deaminase deficiency?• It’s an inherited disorder that damages the immune

system by not producing an important enzyme. This made her immune system weak and vulnerable to nearly every virus.

What the doctors did ?

1-They extracted some of the girl's white blood cells.

2-Then, they exposed them to a genetically engineeredvirus carry normal versions of the gene that was not

3-The virus invaded the white blood cells, andthen these cells were transfused back into the girl.

functioning correctly in the girl.

What happened after that?

Gene therapy helped her to produce the enzyme. So it was a success.

Today Ashanti De Silva is alive…

2-Case of Gene Therapy that went wrong

Jesse Gelsinger

The first documented deathas a result of gene therapy.

What was the problem?

• Gelsinger suffered from :• a rare metabolic disorder called OTC (ornithine

transcarbamylase deficiency).

• What is OTC?• is an inherited disorder that causes ammonia to

accumulate in the blood.

What the doctors did ?

• Replaced his defective genes with a healthy one by a vector.

• He suffered symptoms that had never been seen in other clinical tests that had been performed on (mice, and another human).

• He had a:

What happened after that?

1. blood-clotting disorder.2. function loss of: kidney, lungs, and brain.As a result he died.

• Doctors are still not sure exactly what happened, but they suspected that he went through reaction with the vector.

Objective 6

ETHICAL ISSUES SURROUNDING GENE

THERAPY.

• Because gene therapy involves making changes to the body’s set of basic instructions, it raises many unique ethical concerns. The ethical questions surrounding gene therapy include

Ethical Issues Surrounding Gene Therapy

Ethical Issues Surrounding Gene Therapy

• 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?

• The idea of germline gene therapy is controversial. While it could spare future generations in a family from having a particular genetic disorder, it might affect the development of a fetus in unexpected ways or have long-term side effects that are not yet known. Because people who would be affected by germline gene therapy are not yet born, they can’t choose whether to have the treatment.

Ethical Issues Surrounding Gene Therapy

• Because of these ethical concerns, the U.S. Government does not allow federal funds to be used for research on germline gene therapy in people.

Ethical Issues Surrounding Gene Therapy

• However, germ line therapy is not permitted in any county, on the basis that it is unethical.

1. Give a chance of a normal life to a human born with a genetic disease.

2. Give hope of healthy life to cancer patient.

3. For certain disease that do not have any cure except gene therapy, it could save many lives.

Advantages of Gene Therapy

1- The cost is very high.

2-Unwanted immune system reaction.

3-Targeting the wrong cells.

4-Multigene disorders.

5-Viral vectors problems.

Disadvantages and Risks of Gene Therapy

• http://www.mayoclinic.org/tests-procedures/gene-therapy/basics/definition/prc-20014778

• http://ghr.nlm.nih.gov/handbook/therapy

• http://gene-therapy.yolasite.com/ethics.php

References

Thank you

PREPARED BY: 3RD YEAR MEDICINE STUDENTS IN KING

ABDULAZIZ UNIVERSITY.