Synthesis And Characterization Of A Physically Entangled Dna Hydrogel And Its Applications
DNA is commonly viewed as a genetic material in all life forms, which is responsible for storing and encoding genetic information. However, from a materials perspective, DNA is an inherently generic polymeric material. Since this generic material is derived from biology, it has many unique properties that are not possessed by any other materials, including molecular recognition capability, defined base composition, and precise manipulation by enzymes. These properties have enabled extensive usage of DNA in nanotechnology for creating delicate DNA nanostructures as well as assembling nanomaterials. For real-world applications, however, it is necessary and important to create DNA materials in bulk-scale. Therefore, special attention needs to be paid to the efficiency and the yield for the synthesis of DNA materials. Unfortunately, these two objectives have not been fully explored in the field. In this thesis, I present a novel method to create a bulk-scale physically entangled DNA hydrogel. By designing two enzymatic processes, rolling circle amplification and multi-primed chain amplification, DNA chains are greatly amplified, both in length and in quantity, to entangle with each other to form a DNA hydrogel. Due to the power of enzymatic amplification, a bulk-scale hydrogel is easily produced with low cost and readily to be scaled up. Interestingly, our DNA hydrogel possesses properties that are not found in nature of any kind: it has both solid-like and liquid-like properties. When the gel is immersed in water, it memorizes its original shape and behaves like a solid. However, the hydrogel become free-flowing "liquid" after taken out of water, and metamorphoses back to its original shape upon addition of water. More interestingly, the hydrogel is composed of uniformly sized DNA microspheres. To our surprise, the DNA density in each microsphere reaches as high as the human chromosome density. Thus, the DNA microsphere effectively concentrates unprecedentedly high dose DNA drugs that have never been achieved. This supercondensed ultra-high dose DNA effectively protects the condensed DNA, efficiently enters the cell and releases the DNA, enabling a superior therapeutic effect. This condensed DNA format is potential to serve as a versatile platform to compact and deliver all DNA-based therapeutics.
DNA material; DNA hydrogel
March, John C; Hui, Chung-Yuen
Agricultural and Biological Engineering
Ph. D., Agricultural and Biological Engineering
Doctor of Philosophy
dissertation or thesis