Gene Therapy To Treatment Human Disease

Group 6 Triu Thy Vy Hunh M Hnh H Th Thu Trang Nguyn Th Hng Nhung V Hang Phng Trm

Outline
1. Introduction 2. Classification Germ line gene therapy Somatic gene therapy 1. Vectors- Advantage and disadvantage of gene therapy 2. Future

I. Introduction

What is Gene Therapy

A technique for correcting defective genes that are responsible for disease development There are four approaches:
1. 2. 3. 4. A normal gene inserted to compensate for a nonfunctional gene. An abnormal gene traded for a normal gene An abnormal gene repaired through selective reverse mutation Change the regulation of gene pairs

How Does Gene Therapy Work?

In most gene therapy studies, a "normal" gene is inserted into the genome to replace an "abnormal," disease-causing gene. A carrier molecule called a vector must be used to deliver the therapeutic gene to the patient's target cells. The most common vector is a virus that has been genetically altered to carry normal human DNA. Viruses have evolved a way of encapsulation and delivering their genes to human cells in a pathogenic manner. Scientists manipulate the virus genome to remove disease-causing genes and insert therapeutic ones.

How Does Gene Therapy Work?

Non-viral options:
Direct introduction of therapeutic DNA into target cells. Can be used only with certain tissues and requires large amounts of DNA. An artificial lipid sphere with an aqueous core, called a liposome, which carries the therapeutic DNA, is capable of passing the DNA through the target cell's membrane.

II. Classification
Germ line gene therapy Somatic gene therapy
Ex vivo In vivo

Germ line gene therapy

Germ cells (sperm, eggs) are modified by the introduction of functional genes, which are ordinarily integrated into their genomes. The change due to therapy would be heritable and passed on to later generations. Prohibited for application in human beings.

Germ line gene therapy

Commonly used in:
Treating a pre-embryo that carries a serious genetic defect before implantation into the mother Treating the germ cells (sperm or egg cells) of the afflicted adults so that their genetic defects would not be passed on to their offspring

Germ line gene therapy

Arguments specifically against germline therapy include: Involves too much scientific uncertainty and risk. Research on early embryos, such research essentially creates generations of unconsenting research subjects Violate the rights of subsequent generations to inherit a genetic endowment that has not been

Germ line gene therapy

Arguments in favor of germline gene therapy: Efficient: prevent cancers, treat genetically defective embryos Unique disease: hereditary diseases of the central nervous system

Somatic gene therapy

Somatic gene therapy is the transfer of genes into the somatic cells of the patient The gene transfer transferred - normal alleles that could correct the mutant or disease alleles It affects only the targeted cells in the patient, and is not passed on to future generations

Types of somatic gene therapy

Ex vivo In vivo
interio

exterior

the cells are treated outside the body

the gene is transferred to cells inside the patient's body

Cystic Fibrosis (Pulmonary diseases)

Diabetes type I (kidney disease)

Malignant brain tumors

Somatic gene therapy

Advantages Less controversial than germ line gene therapies. Disadvantages If a treatment or cure is successful , it will not be passed on to the patient/organism's offspring. The methodology of somatic gene therapy, such as the use of viral vectors, is difficult.

III. Vectors- Advantage and Disadvantage of gene therapy

Vectors
Vectors are carrier molecules which are employed to enhance gene transfer efficiency in gene therapy In optimizing a particular vector, one must consider: Host immune response Must target specific tissues for long term gene expression Regulation of the gene after insertion Both viral and non-viral vectors have been

Viral vectors
Viral vectors use viral genome to carry therapeutic gene(s) and to infect human body cells Adenovirus (common cold) Adeno-Associated Virus Retrovirus (HIV) Herpes simplex virus (cold sores)

Viruses must be engineered so that they can neither produce disease not spread (extremely effective at infecting human cells)

Vector Transfection
Targeted gene therapy may result since some viruses infect certain body cells Adenoviruses infect both dividing & nondividing cells effectively Retroviruses are of interest because they insert DNA into the genome of host where it remains permanently (integration), but often, randomly

Vector Transfection
Herpes virus (HSV-1) strain primarily affects central nervous system (CNS)
May help develop treatments for Alzheimers, Parkinsons, and other genetic neurodegenerative diseases.

Adeno-Associated viruses do not cause illness in humans, caan infect a wide variety of cells, & integrate 95% of time in same location However, although viral vectors may help, most human cells are not easily transfected

Disadvantages of Gene Therapy

Short Lived Hard to rapidly integrate therapeutic DNA into genome and rapidly dividing nature of cells prevent gene therapy from long time Would have to have multiple rounds of therapy Immune Response new things introduced leads to immune response increased response when a repeat offender enters Viral Vectors patient could have toxic, immune, inflammatory response also may cause disease once inside Multigene Disorders Heart disease, high blood pressure, Alzheimers, arthritis and diabetes are hard to treat because you need to introduce more than one gene May induce a tumor if integrated in a tumor suppressor gene because insertional mutagenesis

Advantages of Gene Therapy

Give a chance of a normal life to baby born with genetic disease. Give hope of healthy life to cancer patient. For certain disease that do not have any cure except gene therapy, it could save many lives

IV. The Future of Gene Therapy

 With its potential to eliminate and prevent hereditary diseases and its use as a possible cure for heart disease, AIDS, and cancer. It may be possible to treat an unborn child for a genetic disease even before symptoms appear. And also maybe the cardiovascular diseases, monogenic diseases and the hemophilia be treated. Gene therapy is a potential medical miracle-worker

References

http://www.ndsu.edu/pubweb/~mcclean/plsc431/students/bran

http://www.ornl.gov/sci/techresources/Human_Genome/medicin http://www.medindia.net/articles/genetherapy_treatment.htm http://dna-bio.blogspot.com/ http://www.angelfire.com/hi3/germline/

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