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

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

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

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

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

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

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