Lecture on Structural DNA Nanotechnology

Presenter

• Name: William Shei
• Title: Associate Professor of Biological Chemistry and Molecular Pharmacology
• Affiliations: Harvard Medical School, Dana Farber Cancer Institute, VIS Institute for Biologically Inspired Engineering

Overview

• Main Topic: Recent advances in structural DNA nanotechnology
• Purpose: Using DNA as a building material to construct nanoscale objects.

Introduction to DNA Nanotechnology

• Traditional DNA Role: Information repository for coding protein sequences and regulation.
• New Focus: Using DNA to construct nanoscale objects (e.g., DNA-designed structures like a Pac-Man shape designed to interact with actin filaments).

Key Concepts and Objectives

• Complementarity: DNA nanostructures leverage the complementarity between DNA base pairs.
• Challenges and Progress: Surpassing perceived limitations of DNA in constructing complex structures.

Recent Developments

• Design and Assembly: Enhancements in designing and assembling DNA nanostructures up to 30 nanometers in diameter.
• Goal: Self-assemble objects with increased complexity and unique components.

Applications

• Molecular Biophysics: Tools for understanding molecular behaviors at the nanoscale.
• Therapeutics: Potential applications in future medical treatments.
• Living Systems Inspiration: Emulating biological processes like building, adapting, healing, and reproducing at the molecular scale.

Key Historical Advances

• Ned Seeman: Father of DNA nanotechnology; created early DNA cubes and porous crystals.
• Key Structures: DNA cube (1992), more complex wireframe structures.
• Holiday Junctions: Key motif for building complex DNA structures.

Methods in DNA Nanotechnology

• DNA Origami: Developed by Paul Rothemund (2006), folding long single strands (e.g., M13 bacteriophage genome).
• Folding Techniques: Heating and cooling processes to achieve the desired structure.
• Structural Complexity: Creating 2D and 3D shapes; emphasis on mastering structural complexity before functional complexity.

Construction Techniques

• Sticky Ends & Branch Junctions: Creating rigid building blocks from DNA.
• Two-Dimensional Crystals: Using tiles and sticky ends to self-assemble complex patterns.
• Three-Dimensional Shapes: Inspired by paper origami, creating complex 3D shapes like boxes and honeycombs.

Software and Tools

• CAD Nano: Software suite developed to facilitate design and ensure robust assembly of DNA nanostructures.

Future Directions

• Scaling Complexity: Addressing self-assembly errors, improving yield, and hierarchical methods to create larger, more complex structures.
• Applications in Medicine: Potential for regenerative medicine and tissue engineering through mechanical and biochemical responses.

Conclusion

• Versatility of DNA: DNA origami as a powerful method for molecular-scale engineering.
• Ongoing Research: Continuous effort to enhance techniques and explore new applications.