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Protein delivery: DNA nanostructures and cell-surface targeting Harvard iGEM August 27, 2006 The Machine Goal: Future modularized drug delivery target cell DNA Nanostructures Overview Can design DNA double helices to stick together and form interesting structures. Dr. Ned Seeman, NYU Dr. William Shih, Harvard Paul Rothemund, Caltech A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron WILLIAM M. SHIH, JOEL D. QUISPE & GERALD F. JOYCE Nature 427, 618ミ621 (2004); doi:10.1038/nature02307 Motivation: Why DNA? Fascinating area of research The power of DNA Watson-Crick base pairing is enormously strong Self-assembly Highly programmable, designable Specificity - targeting to cells Design Details Design Details: Scaffolded Oragami Design Details: Scaffolded Oragami Design Details: Scaffolded Oragami Design Details: Positional Control Design Details: Positional Control Design Details: Positional Control Design Details: Positional Control Design Details: Positional Control Design Details: Positional Control Progress Built a number of barrel designs Exciting EM Images Purifying Nanostructures (nearly there after 1 month of trials) Exciting EM Images Exciting EM Images EM Images (snakes on a grid) Images courtesy Shawn Douglas c5.0 barrel (10 nM), 0.7% uranyl formate Appear to be lining up end to end, probably because of the stain To be continued Can a protein be protected from protease if attached inside the box? Lid attachment Lid removal protein protease protease protein Acknowledgements Harvard TFs - Shawn Douglas, Nick Stroustrup, Chris Doucette Harvard advisers - Dr. William Shih, Dr. George Church, Dr. Pamela Silver, Dr. Alain Viel, Jagesh Shah, Dr. Radhika Nagpal iGEM ambassadors iGEM directors Dr.