2005 US Frontiers of Science Symposium

2005 US Frontiers of Science Symposium

Applications of RNAi in Mammalian Genetics and Therapy

Greg Hannon, Cold Spring Harbor Laboratory

1. Applications of RNAi in
Mammalian Genetics and Therapy

2. How can we trigger RNAi in mammals?

3. Our approach : provide a new microRNA gene :
shRNAs or Short Hairpin RNAs

4. Short-hairpin actived gene silencing (Shagging)

5. How do we get those new genes into cells?

6. RNAi as a Genetic Tool

8. Genome-wide RNAi Libraries

9. Genome-wide RNAi Libraries

10. Genome-wide RNAi Libraries

11. Genome-wide RNAi Libraries

12. shRNA^mir libraries :
enabling genetics in mammalian cells

13. Using RNAi to study gene function

14. Shutting off a tumor suppressor gene

15. Turning off genes in animals

16. B-cell lymphoma model

17. What are the effects of shutting down p53?

18. Controlling suppression – regulating shRNAs with drugs

19. Regulate the tumor suppressor, regulate the phenotype

20. Regulate the tumor suppressor, regulate the phenotype

21. Tumor formation in mice

22. What happens to tumors if we shut off the shRNA?

23. Cancer genetics in mammalian cells identifying new targets

24. Identifying Anti-Cancer Targets

25. Searching for drug synergy

26. Many common
Chemotherapeutics
act via p53

27. Output : Therapy kills cancer cells

28. Increasing sensitivity via the p53 pathway
would lower therapeutic dose and reduce side effects.

29. Can we modulate the p53 response?

30. Searching for drug synergy

31. pSM2-shRNA cassette

33. Tarceva treated at low dose

34. Loss of some
genes enhances
drug sensitivity

35. Drug Synergy

36. Can RNAi be used directly as a therapy?

37. Hydrodynamic Transfection in Mice

38. siRNAs in vivo

41. Plasma apoB-100 levels

42. Cholesterol Levels

45. Collaborators

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Copyright © 2005. National Academy of Sciences. All rights reserved.