Protein delivery: DNA nanostructures and cell-surface targeting

Harvard iGEMAugust 27, 2006

The Machine Goal: Future modular drug delivery

drug

target cell

Molecular containers in nature Hard to duplicate artificially

http://micro.magnet.fsu.edu/cells/viruses/images/virus.jpghttp://www.biology4kids.com/files/art/cell_over1.gif

DNA Nanostructures Overview

DNA can be used to approximate arbitrary 3D structures

WILLIAM M. SHIH, JOEL D. QUISPE & GERALDF. JOYCENature 427, 618 ﾐ 621 (2004);

http://www.dna.caltech.edu/~pwkr/

William Shih, Harvard Ned Seeman, NYU Paul Rothemund, Caltech

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

Design Details: Scaffolded Oragami

When the sample reaches room temperature (2hrs later), the origami have folded

http://www.dna.caltech.edu/~pwkr/

Design Details: Positional Control

Design DetailsDouble-ply barrel and lid

Lid: 33 nm across, 28 nm longBarrel: 27.5 nm long, 27.6 nm across

Exciting EM Images

Exciting EM Images

To be continued

Can a protein be protected from protease if attached inside the box?

Lid attachment Lid removal

protein

protein

protease

protease

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