Hierarchical Self-assembly of Novel DNA Nanostructures for Biomedical and Biomimetic Research Open Access

Abstract

Structural DNA nanotechnology has been extensively utilized for the self-assembly of an unprecedented number of nanostructures in past decades. However, the pursuit of novel assembly mechanisms and scaling methods of DNA nanostructures has never ended. In this dissertation, we introduce our effort on several challenging projects focusing on this pursuit in structural DNA nanotechnology. Chapter 1 of this dissertation introduces the current state of structural DNA nanotechnology, the challenges that remain unsolved, and the significance of the contribution to solving these challenges. Chapter 2 describes a novel amphiphilic spherical micelle/nanorod assembly from cholesterol-DNA block copolymer. The hierarchical assembly mechanism from spherical micelles to nanorods provides brand new inspiration for future amphiphilic DNA block copolymer design. Chapter 3 describes a simple yet versatile method for the scaling of DNA nanotubes into micrometer-scale rigid DNA bundles. The constructed DNA bundles are reconfigurable and possess high programmability, which allows applications in nanofabrication and biomimetic research. Chapter 4 summarizes the work covered in this dissertation in detail, and also briefly introduces other selected projects that have been conducted during the graduate study.

Table of Contents

Chapter 1. Introduction of structural DNA nanotechnology

1.1 Structural DNA nanotechnology

1.1.1 Introduction

1.1.2 Methods for DNA nanostructure construction

1.2 Applications of structural DNA nanotechnology

1.2.1 Dynamic DNA nanostructures

1.2.2 Nanofabrication

1.2.3 Drug delivery

1.3 Challenges and perspectives of structural DNA nanotechnology

1.3.1 Scaling up DNA nanostructures

1.3.2 Optimization on drug delivery systems

1.3.3 From multi-stranded to single-stranded, from DNA to RNA

1.4 Other nucleic acid-related backgrounds involved in this thesis

1.4.1 DNA strand displacement

1.4.2 RNA transcription and Central dogma

1.4.3 Aptamer

1.5 References

Chapter 2. Hierarchical Self-Assembly of Cholesterol-DNA Nanorods

2.1 Abstract

2.2 Background

2.2.1 DNA block copolymers in DNA nanotechnology

2.2.2 DBC nanostructures as drug delivery agents

2.2.3 Hypothesis and goal of this project

2.3 Results and discussion

2.3.1 General design of chol-DNA DBCs and characterization of micellular nanostructures

2.3.2 Factors influencing the morphology of assembled structures

2.3.3 Mechanism of the transition from spherical micelles to nanorods

2.4 Conclusion

2.5 Material and Methods

2.6 Reference

Chapter 3. Building Large DNA Bundles via Controlled Hierarchical Assembly of DNA Tubes

3.1 Abstract

3.2 Background

3.2.1 Bundle fiber structures in nature

3.2.2 The effort of using DNA nanotechnology in building bundle fiber structures

3.2.3 DNA DX tile structure

3.2.4 Hypothesis and goal of this project

3.3 Results and discussion

3.3.1 General design and characterization of DNA bundles

3.3.2 Inserted cohesive linker's influence on DNA bundle assembly

3.3.3 Reaction condition's influence on DNA bundle assembly

3.3.4 DNA bundles of prescribed features assembled from multiple components

3.3.5 Reconfiguration of DNA bundles

3.4 Conclusion

3.5 Material and Methods

3.6 References

Chapter 4. Summary and other projects

4.1 Summary for the thesis

4.2 Future perspectives of the thesis

4.2.1 Hierarchical Self-Assembly of Cholesterol-DNA Nanorods

4.2.2 Building Large DNA Bundles via Controlled Hierarchical Assembly of DNA Tubes

4.3 Other projects related to the application of structural DNA nanotechnology in biomedical research

4.3.1 Development of novel dual-targeting immune checkpoint inhibitors for cancer therapy using DNA nanotechnology   

4.3.2 Programmable site-specific functionalization of DNA origami with polynucleotide brushes

4.3.3 Systemic delivery of Bcl2-targeting shRNA by single-stranded RNA nanoparticles

4.4 References

About this Dissertation

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School	Laney Graduate School
Department	Chemistry
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Biology, Molecular Nanoscience Chemistry, Biochemistry
Keyword	Molecular Biology DNA nanotechnology DNA origami
Committee Chair / Thesis Advisor	Yonggang Ke, Emory University
Committee Members	David Lynn, Emory University Vincent Conticello, Emory University

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