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Chemical Engineering of Nanomaterials for the Delivery of Biomolecular Cargo

Abstract

Nanomaterials have the potential to play a significant role in the development of new biotechnology for diverse applications, including agricultural genetic engineering, biological sensing, nanomedicine, optics, and more. Therefore, a robust, fundamental understanding of their material properties and the techniques to engineer these properties is a key area of scientific interest.

In this dissertation, we explore several key areas where the chemical engineering of nanotechnology, particularly single walled carbon nanotubes (SWNTs), can have a significant impact. We first broadly explore emerging trends in some of the most promising near-infrared luminescent materials and applications. In particular, we focus on how a more comprehensive understanding of their intrinsic material properties might allow researchers to better leverage these traits for innovative and robust applications.

Further, we focus on the ways in which nanomaterials can address some of the most critical challenges of CRISPR genome editing in plants through improvements in cargo delivery, species independence, germline transformation and gene editing efficiency. We identify major barriers preventing CRISPR-mediated plant genetic engineering from reaching its full potential, and discuss ways that nanoparticle technologies can lower or eliminate these barriers.

Next, we present mechanisms to optimize DNA loading on SWNTs with a library of polymer- SWNT constructs and assess DNA loading ability, polydispersity, and both chemical and colloidal stability. We demonstrate that polymer hydrolysis from nanomaterial surfaces can occur depending on polymer properties and attachment chemistries, and we describe mitigation strategies against construct degradation. Given the growing interest in delivery applications in plant systems, we also assess the stress response of plants to polymer-based nanomaterials and provide recommendations for future design of nanomaterial-based polynucleotide delivery strategies.

We then adapt our findings from the development of polymer-SWNTs towards the synthesis of protein-functionalized SWNTs and the covalent attachment of DNA cargo. Specifically, we explore the development of streptavidin-biotin chemistry as a potential alternative to other existing nanoparticle-biomolecule delivery systems and offer exciting opportunities for future research.

Finally, we explore the federal regulatory challenges in the United States that limit scientific innovation and unduly hinder the widespread production of genetically engineered crops, like those we propose to develop throughout this thesis. To address these shortcomings, we propose policy recommendations including the consolidation of federal regulatory communication and a unified web platform for commercial approval applications.

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