SUICIDE GENE THERAPY

1. SUICIDE GENE THERAPY By: Antonio Alatorre Raquel Abella Chrissy Kachinoski Nicole Fowler Tracy Mesina

2. Technique first used in 1992 • Ashanti Disilva was afflicted with ADA • Doctors inserted ADA gene into her bone marrow cells • Doctors used suicide genes to kill those cells containing ADA if they negatively affected her body • The cells could be killed with ganciclovir

3. Development • The herpes simplex thymidine kinase gene is susceptible to treatment with ganciclovir • Human thymidine kinase gene is not susceptible to the drug • The adenovirus was the chosen vector because it only infects rapid growing cells

4. The Process • The herpes simplex virus thymidine kinase gene is injected into tumor cells via an adenovirus vector • This gene causes the cells to produce thymidine kinase • The drug ganciclovir is then administered • This drug is phosphorylated and transformed to poison by thymidine kinase • The poison produced then cripples the tumor cells’ genetic machinery

5. The Story of Joe HillFirst Cancer Use • Joe was afflicted with cancer of the brain • Doctors infected his tumor cells with an adenovirus vector carrying a thymidine kinase gene • The virus was injected into five sites of Joe’s tumor • One week later, Joe was administered ganciclovir

6. The Story of Joe Hill • After a week, the tumor was removed • Doctors found that only approximately 1 in 10 of the tumor cells were infected with the adenovirus • However, ten times that many tumor cells actually died • This was a result of the bystander effect

7. Key Points: • Bystander Effect: The effects of the adenovirus affects neighboring cells • This therapy is being used for many kinds of cancer at present, not just brain cancer