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 modularized drug delivery

target cell
protein
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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?621
(2004) doi10.1038/nature02307
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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

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Design Details
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Design Details Scaffolded Oragami
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Design Details Scaffolded Oragami
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Design Details Scaffolded Oragami
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Design Details Positional Control
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Design Details Positional Control
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Design Details Positional Control
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Design Details Positional Control
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Design Details Positional Control
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Design Details Positional Control
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Progress

• Built a number of barrel designs
• Exciting EM Images
• Purifying Nanostructures (nearly there after 1
  month of trials)

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Exciting EM Images
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Exciting EM Images
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EM Images (snakes on a grid)

• c5.0 barrel (10 nM), 0.7 uranyl formate
• Appear to be lining up end to end, probably
  because of the stain

Images courtesy Shawn Douglas
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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