Gene Therapy

1. Gene Therapy Kortlynn Johnson

2. What is Gene Therapy? • A technique for correcting defective genes responsible for disease development1

3. Correcting Faulty Genes Doctors may use 1 of these approaches1: • A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. • *Most common* • An abnormal gene could be swapped for a normal gene through homologous recombination. • The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function. • The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered.

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 Vectors1 • 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 Vectors1 • 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 Approaches1 • 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 Approaches1 • 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 Therapy1 • 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 Therapy1 • 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 Global1 • 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 Global1 • 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 Global1 • 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 Therapy1 • 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 Therapy5 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 • http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml#whatis • http://www.unitedspinal.org/publications/action/wp-content/gene-therapy.jpg • http://www.nature.com/gt/journal/v13/n18/images/3302838f1.jpg • http://www.newscientist.com/article/dn2878-miracle-gene-therapy-trial-halted.html • http://www.ndsu.edu/pubweb/~mcclean/plsc431/students/eric.htm