IGEM:Harvard/2006/DNA nanostructures

Project Overview

• Our goal is to to design and implement molecular containers, which can be dynamically opened and closed by an external stimulus.
• The containers will be implemented as DNA nanostructures, which afford a significant degree of positional control and chemical versatility.
• As an initial proof-of-concept, we plan to use our DNA containers to demonstrate controllable activation ("delivery") of anti-thrombin aptamers.
• We expect that molecular containers could have several interesting scientific and clinical applications, such as
  • Drug and gene delivery
  • Bio-marker scavenging (early detection of biomarkers)
  • Directed evolution (compartmentalized selections)
  • Using multiplexing for combinatorial chemical synthesis
  • Capture and stabilization of multiprotein complexes
  • Protein folding (chaperones)
  • Cell sorting

Container Specs

Container Designs

• 

  Design 1
  hexagonal core, separate 1-ply lids

• 

  Design 2
  hexagonal core, separate 2-ply lids

• 

  Design 3
  rectangular core, continuous 1-ply lids

• 

  Design 4
  hexagonal core, separate 1-ply lids

Latch Designs

• 

  latch1
  (ai file)

• 

  latch2
  (ai file)

Coding

Existing code

• William's code (Python)

Thrombin-aptamer experiments

Notes

Buffers

• Macaya's and Bock's selection buffer: 20 mM Tris-acetate, pH 7.4, 140 mM NaCl / 5 mM KCl / 1 mM CaCl₂ / 1 mM MgCl₂

Bibliography

1. Schultze P, Macaya RF, and Feigon J. Three-dimensional solution structure of the thrombin-binding DNA aptamer d(GGTTGGTGTGGTTGG). J Mol Biol. 1994 Feb 4;235(5):1532-47. DOI:10.1006/jmbi.1994.1105 |
2. Liu Y, Lin C, Li H, and Yan H. Aptamer-directed self-assembly of protein arrays on a DNA nanostructure. Angew Chem Int Ed Engl. 2005 Jul 11;44(28):4333-8. DOI:10.1002/anie.200501089 |
3. Li WX, Kaplan AV, Grant GW, Toole JJ, and Leung LL. A novel nucleotide-based thrombin inhibitor inhibits clot-bound thrombin and reduces arterial platelet thrombus formation. Blood. 1994 Feb 1;83(3):677-82.
4. Bock LC, Griffin LC, Latham JA, Vermaas EH, and Toole JJ. Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature. 1992 Feb 6;355(6360):564-6. DOI:10.1038/355564a0 |
5. Macaya RF, Schultze P, Smith FW, Roe JA, and Feigon J. Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3745-9. DOI:10.1073/pnas.90.8.3745 |

Presentations

Most recent (Week 3)

• Week 3 Presentation: Design Progress

Week 2: Original proposal

• Presentation Proposal

Working Team Members

• Tiffany Chan (talk)
• Katherine Fifer (talk)
• Valerie Lau (talk)
• Matthew Meisel (talk)
• ...and others are welcome!