gene treatment and rules for gene treatment.pptx

gene treatment and rules for gene treatment

1. Gene Therapy Biosafety & Bioethics

2. Gene therapy is the introduction of genes into existing cells to prevent or cure a wide range of diseases. It is responsible for correcting defective genes responsible for disease development. The first approved gene therapy experiment Occurred on September 14, 1990 . Introduction

3. Somatic cell Gene Therapy Types Of Gene Therapy Somatic Cell Gene Therapy Germ line Gene Therapy Therapeutic genes transferred into the somatic cells. E.g. Introduction of Genes into bone marrow cells, blood cells, skin cells etc. Will not be inherited later generations. At present all researches directed to correct genetic defects in somatic cells. Therapeutic genes transferred into germ cells. E.g. Genes introduced into eggs and sperms. It is heritable and passed on to later generations. For safety, ethical and technical reasons, it is not being attempted at present.

4. Types Of Somatic Cell Gene Therapy Ex vivo Cells are modified outside the body and then transplanted back in again Called ex vivo because the cells are treated outside the body In vivo Genes are changed in cells when the cells are still in the body Called in vivo because the gene is transferred to cells inside the body

5. Ex vivo and In vivo Gene Therapy

6. Ex vivo Gene Therapy Isolate cells with genetic defect from a patient Grow the cells in culture Introduce the therapeutic genes Select genetically corrected cells and grow Transplant the modified cells to the patient

7. 1 st gene therapy- to correct deficiency of enzyme, Adenosine deaminase (ADA). Performed on a 4 year old girl Ashanthi Desilva. Was suffering from SCID- Severe Combined Immunodeficiency. Caused due to defect in gene coding for ADA. Deoxy adenosine accumulate and destroys T lymphocytes. Disrupts immunity, suffer from infectious diseases and die at young age. Examples Of Ex vivo Gene Therapy

8. Ex vivo Ex Vivo

9. In Vivo Gene Therapy Direct delivery of therapeutic gene into target cell into patients body. Carried out by viral or non viral vector systems. It can be the only possible option in patients where Individual cells cannot be cultured in vitro in Sufficient numbers (e.g. brain cells). In vivo gene transfer is necessary when cultured cells cannot be re- implanted in patients effectively. In Vivo Gene Therapy

10. Example of In vivo Gene Therapy Therapy for cystic fibrosis Example of In Vivo Gene Therapy Therapy for cystic fibrosis In patients with cystic fibrosis , a protein called cystic fibrosis transmembrane regulator (CFTR) is absent due to a gene defect. In the absence of CFTR chloride ions concentrate within the cells and it draws water from surrounding. This leads to the accumulation of sticky mucous in respiratory tract and lungs. Treated by in vivo replacement of defective gene by adenovirus vector.

11. In Vivo

12. Vectors for Gene Therapy The Ideal Vector Safe Transfection efficient Selective Persistent gene transfer Unrecognized by immune system Vectors For Gene Therapy

13. Different carrier systems are used for gene delivery. Vectors in Gene Therapy

14. Physical Microinjection Electroporation Sonoporation Gene Gun Advantages: Disadvantages : - Effective in transfecting primary, progenitor and stem cells. -Cell may sustain heavy trauma and initiate apoptotic mechanisms. - Requires high precision and accuracy for success.

15. Chemical Oligonucleotides Liposomes Dendrimers Calcium Phosphate Advantages: - Target ligand ensures delivery to correct cells. very effective at targeting cancer cells. Disadvantages: -Effective doses can be toxic. - Difficulty transfecting primary, progenitor and stem cells.

16. Biological Retrovirus Adenovirus Adeno associated Virus Herpes Simplex Virus Advantages : Disadvantages : - Integrates into cell efficiently -High expression of therapeutic gene -Immune reactions -May reactive in the body - Transfecting wrong cells.

17. Ethical Issues Gene therapy involves making changes to the body‟s set of basic instructions, it raises many unique ethical concerns. Ethical questions surrounding gene therapy include : How can “good” and “bad” uses of gene therapy be distinguished? Who decides which traits are normal and which constitute a disability or disorders? 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?

18. Successfully Treated Diseases with Gene Therapy Gene therapy is still considered an experimental discipline. Cystic fibrosis Haemophilia Thalassemia Sickle Cell Anemia Severe Combined Immunodeficiency

19. Advantages & Disadvantages of Gene Therapy Advantages Disadvantages Can be used to „silence‟ a disease before its onset. E.g. HIV in AIDS Potential to eliminate and prevent hereditary diseases. The “Last Chance” or “Last Hope” therapy. Achieving pharmaceutical effects E.g. Making cancer cells susceptible to anticancer drugs Short- lived nature Repeated therapy Severe Adverse Effects E.g. Viral vectors may trigger an extreme immune response Viral vectors could recover the ability to cause disease once inside the patient. Insertional mutagenesis (Virus targets wrong cell new disease occur) Difficulty to effectively treat multigenic disorders E.g. Diabetes, Heart Disease.