1. Kortlynn Johnson

2. What is Gene Therapy? A technique for correcting defective genes responsible for disease development 1

3. Correcting Faulty Genes 1. A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. *Most common* 2. An abnormal gene could be swapped for a normal gene through homologous recombination. 3. The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function. 4. The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered. Doctors may use 1 of these approaches 1 :

4. How Does Gene Therapy Work? 1 In most gene therapy studies, a "normal" gene is inserted into the genome to replace an "abnormal," disease-causing gene. Carrier molecule  Vector Most common carrier  Virus

5. A Vector in ACTION!!! 2

6. Types of Vectors 1 Retroviruses Create double-stranded DNA copies of their RNA genomes These copies of its genome can be integrated into the chromosomes of host cells Adenoviruses Have double-stranded DNA genomes that cause respiratory, intestinal, and eye infections in humans.

7. Types of Vectors 1 Adeno-associated viruses Small, single-stranded DNA viruses that can insert their genetic material at a specific site on chromosome 19 Herpes simplex viruses Double-stranded DNA viruses that infect a particular cell type – neurons

8. Non-Viral Approaches 1 Direct introduction of therapeutic DNA into target cells Simplest method This approach is limited in its application because it can be used only with certain tissues and requires large amounts of DNA.

9. Non-Viral Approaches 1 Another nonviral approach involves the creation of an artificial lipid sphere with an aqueous core. This liposome, which carries the therapeutic DNA, is capable of passing the DNA through the target cell's membrane.

10. Non-Viral Approach (Liposome Method) 3

11. Applications of Gene Therapy 1 Current Researchers also are experimenting with introducing a 47th (artificial human) chromosome into target cells. This chromosome would exist autonomously alongside the standard 46 --not affecting their workings or causing any mutations.

12. Applications of Gene Therapy 1 It would be a large vector capable of carrying substantial amounts of genetic code, and scientists anticipate that, because of its construction and autonomy, the body's immune systems would not attack it. **A problem with this potential method is the difficulty in delivering such a large molecule to the nucleus of a target cell.**

13. Gene Therapy: Going Global 1 The School of Pharmacy in London is testing a treatment in mice, which delivers genes wrapped in nanoparticles to cancer cells to target and destroy hard-to-reach cancer cells. (March 2009) UK researchers from the UCL Institute of Ophthalmology and Moorfields Eye Hospital NIHR Biomedical Research Centre announced results from the world’s first clinical trial to test a revolutionary gene therapy treatment for a type of inherited blindness. The results show that the experimental treatment is safe and can improve sight. (April 2008)

14. Gene Therapy: Going Global 1 In France, gene therapy performed on children suffering from Severe Combined Immunodeficiency was halted because one of the patients developed leukemia as a direct consequence of the treatment. (October 2002) 4

15. Gene Therapy: Going Global 1 China’s first gene therapy was just recently approved in 2003. China's medicines authority approved the cancer therapy after it achieved promising results in a clinical trial.

16. Setbacks for Advancement… 1 The Food and Drug Administration (FDA) has not yet approved any human gene therapy product for sale.

17. Setbacks for Advancement… 1 In 1999, gene therapy suffered a major setback with the death of 18-year-old Jesse Gelsinger. Jesse was participating in a gene therapy trial for ornithine transcarboxylase deficiency (OTCD). He died from multiple organ failures 4 days after starting the treatment. His death is believed to have been triggered by a severe immune response to the adenovirus carrier.

18. Some Ethical Questions to Consider about Gene Therapy 1 What is normal and what is a disability or disorder, and who decides? Are disabilities diseases? Do they need to be cured or prevented? Does searching for a cure demean the lives of individuals presently affected by disabilities? Preliminary attempts at gene therapy are exorbitantly expensive. Who will have access to these therapies? Who will pay for their use?

19. Pros and Cons of Gene Therapy 5 Pros Cons Wipe out genetic disease before it can begin and eliminate suffering for future applications Good technique for diseases not researched yet People carry defected genes and may be unaware Gene therapy can eliminate the consequences of carrying these genes Putting human fate into our own hands Creating a “superior race” “Playing God”

20. References 1. http://www.ornl.gov/sci/techresources/Human_Gen ome/medicine/genetherapy.shtml#whatis http://www.ornl.gov/sci/techresources/Human_Gen ome/medicine/genetherapy.shtml#whatis 2. http://www.unitedspinal.org/publications/action/w p-content/gene-therapy.jpg http://www.unitedspinal.org/publications/action/w p-content/gene-therapy.jpg 3. http://www.nature.com/gt/journal/v13/n18/images/3 302838f1.jpg 4. http://www.newscientist.com/article/dn2878- miracle-gene-therapy-trial-halted.html http://www.newscientist.com/article/dn2878- miracle-gene-therapy-trial-halted.html 5. http://www.ndsu.edu/pubweb/~mcclean/plsc431/stu dents/eric.htm