Protein delivery: DNA nanostructures and cell-surface targeting

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Protein delivery DNA nanostructures and
cell-surface targeting
Harvard iGEM August 27, 2006
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The Machine

• Goal Future modular drug delivery

target cell
drug
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Molecular containers in nature

• Hard to duplicate artificially

http//www.biology4kids.com/files/art/cell_over1.g
if
http//micro.magnet.fsu.edu/cells/viruses/images/v
irus.jpg
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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 Nature 427, 618?621 (2004)
http//www.dna.caltech.edu/pwkr/
http//seemanlab4.chem.nyu.edu/nano-cube.html
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Motivation Why DNA?

• The power of DNA
• Nanometer scale
• Covalent modifications possible
• Inexpensive synthesis
• Highly programmable/designable

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Design Details Scaffolded Oragami
M13 viral genome 7308 bases long
Add 180 helper strands in Mg buffer
Heat to near boiling. (90 C)
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Design Details Scaffolded Oragami
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Design Details Scaffolded Oragami
When the sample reaches room temperature (2hrs
later), the origami have folded
http//www.dna.caltech.edu/pwkr/
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Design Details Positional Control
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Design Details
Double-ply barrel and lid
Lid 33 nm across, 28 nm long Barrel 27.5 nm
long, 27.6 nm across
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Exciting EM Images
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Exciting EM Images
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To be continued
protease

• Can a protein be protected from protease if
  attached inside the box?
• Lid attachment
• Lid removal

protein
protease
protein
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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