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Protein delivery: DNA nanostructures and cell-surface targeting. Harvard iGEM August 27, 2006. The Machine. Goal: Future modular drug delivery. target cell. drug. Molecular containers in nature. Hard to duplicate artificially. http://www.biology4kids.com/files/art/cell_over1.gif.
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Protein delivery:DNA nanostructures and cell-surface targeting Harvard iGEM August 27, 2006
The Machine • Goal: Future modular drug delivery target cell drug
Molecular containers in nature • Hard to duplicate artificially http://www.biology4kids.com/files/art/cell_over1.gif http://micro.magnet.fsu.edu/cells/viruses/images/virus.jpg
DNA Nanostructures Overview • DNA can be used to approximate arbitrary 3D structures Ned Seeman, NYU Paul Rothemund, Caltech William Shih, Harvard WILLIAM M. SHIH, JOEL D. QUISPE & GERALDF. JOYCE Nature427, 618ミ621 (2004); http://www.dna.caltech.edu/~pwkr/ http://seemanlab4.chem.nyu.edu/nano-cube.html
Motivation: Why DNA? • The power of DNA • Nanometer scale • Covalent modifications possible • Inexpensive synthesis • Highly programmable/designable
Design Details: Scaffolded Oragami M13 viral genome 7308 bases long Add ~180 helper strands in Mg++ buffer Heat to near boiling. (90 C)
Design Details: Scaffolded Oragami When the sample reaches room temperature (2hrs later), the origami have folded http://www.dna.caltech.edu/~pwkr/
Design Details Double-ply barrel and lid Lid: 33 nm across, 28 nm long Barrel: 27.5 nm long, 27.6 nm across
To be continued • Can a protein be protected from protease if attached inside the box? • Lid attachment • Lid removal protease protein 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, Dr. Jagesh Shah, Dr. Radhika Nagpal • iGEM ambassadors • iGEM directors