Spherical nucleic acids (SNAs) comprise a nanoparticle core and a densely packed and highly oriented nucleic acid shell, typically DNA or RNA. They have novel architecture-dependent properties that distinguish them from all other forms of nucleic acids and make them useful in materials synthesis, catalysis, diagnostics, therapeutics, and optics/plasmonics. This book covers over two decades of Dr. Mirkin’s research on SNAs and their anisotropic analogues, including synthesis and fundamental properties, and applications in colloidal crystallization, adaptive matter, and nanomedicine, spanning extra- and intracellular diagnostics, gene regulation, and immunomodulation. It is a reprint volume that compiles 101 key papers from high-impact journals in this research area published by the Mirkin Group at Northwestern University, Illinois, USA, within the International Institute for Nanotechnology, and collaborators. Volume 1 provides an overview and a historical framework of engineering matter from DNA-modified constructs and discusses the enabling features of nucleic acid–functionalized nanomaterials. Volume 2 covers design rules for colloidal crystallization, building blocks for crystal engineering, and DNA and RNA as programmable bonds. Volume 3 discusses colloidal crystallization processes and routes to hierarchical assembly, dynamic nanoparticle superlattices, surface-based and template-confined colloidal crystallization, optics and plasmonics with nanoparticle superlattices, and postsynthetic modification and catalysis with nanoparticle superlattices. Volume 4 covers diagnostic modalities, and intracellular therapeutic and diagnostic schemes based upon nucleic acid–functionalized nanomaterials.

Spherical nucleic acids (SNAs) comprise a nanoparticle core, and a densely packed and highly oriented nucleic acid shell. They have novel structure-dependent properties that differ from those of linear nucleic acids and that makes them useful in chemistry, biology, the life sciences, medicine, materials science, and engineering. This book is a reprint volume that compiles 101 key papers that have been published by the Mirkin Group at Northwestern University, USA, and their collaborators over the past more than two decades. Volume 1 provides an overview and a historical framework of SNAs and discusses their enabling features, which set them apart from all other forms of matter. Volume 2 covers the general design rules for colloidal crystal engineering with DNA, spanning the building blocks and DNA- and RNA-based "programmable bonds" that can be utilized in preparing such structures. Volume 3 continues the discussion of colloidal crystallization processes and routes to hierarchical assembly, featuring dynamic nanoparticle superlattices and lattices prepared on surfaces or via templating strategies, and explores what one can uniquely learn from and do with colloidal crystals prepared from nucleic acid–functionalized nanomaterials in optics, plasmonics, and catalysis. Volume 4 covers the role of SNAs in biomedicine, especially as diagnostic probes both inside and outside of cells, and treatments based on gene regulation and immunotherapy.

Spherical nucleic acids (SNAs) comprise a nanoparticle core and a densely packed and highly oriented nucleic acid shell, typically DNA or RNA. They have novel architecture-dependent properties that distinguish them from all other forms of nucleic acids and make them useful in materials synthesis, catalysis, diagnostics, therapeutics, and optics/plasmonics. This book covers over two decades of the author's research on SNAs and their anisotropic analogues, including synthesis and fundamental properties, and applications in colloidal crystallization, adaptive matter, and nanomedicine, spanning extra- and intracellular diagnostics, gene regulation, and immunomodulation.

"Spherical nucleic acids (SNAs) comprise a nanoparticle core and a densely packed and highly oriented nucleic acid shell. They have novel structure-dependent properties that differ from those of linear nucleic acids that makes them useful in chemistry, biology, the life sciences, medicine, materials science, and engineering." Back cover

Spherical nucleic acids (SNAs) comprise a nanoparticle core, and a densely packed and highly oriented nucleic acid shell. They have novel structure-dependent properties that differ from those of linear nucleic acids and that makes them useful in chemistry, biology, the life sciences, medicine, materials science, and engineering. This book is a reprint volume that compiles 101 key papers that have been published by the Mirkin Group at Northwestern University, USA, and their collaborators over the past more than two decades. Volume 1 provides an overview and a historical framework of SNAs and discusses their enabling features, which set them apart from all other forms of matter. Volume 2 covers the general design rules for colloidal crystal engineering with DNA, spanning the building blocks and DNA- and RNA-based "programmable bonds" that can be utilized in preparing such structures. Volume 3 continues the discussion of colloidal crystallization processes and routes to hierarchical assembly, featuring dynamic nanoparticle superlattices and lattices prepared on surfaces or via templating strategies, and explores what one can uniquely learn from and do with colloidal crystals prepared from nucleic acid–functionalized nanomaterials in optics, plasmonics, and catalysis. Volume 4 covers the role of SNAs in biomedicine, especially as diagnostic probes both inside and outside of cells, and treatments based on gene regulation and immunotherapy.

Spherical nucleic acids (SNAs) comprise a nanoparticle core, and a densely packed and highly oriented nucleic acid shell. They have novel structure-dependent properties that differ from those of linear nucleic acids and that makes them useful in chemistry, biology, the life sciences, medicine, materials science, and engineering. This book is a reprint volume that compiles 101 key papers that have been published by the Mirkin Group at Northwestern University, USA, and their collaborators over the past more than two decades. Volume 1 provides an overview and a historical framework of SNAs and discusses their enabling features, which set them apart from all other forms of matter. Volume 2 covers the general design rules for colloidal crystal engineering with DNA, spanning the building blocks and DNA- and RNA-based "programmable bonds" that can be utilized in preparing such structures. Volume 3 continues the discussion of colloidal crystallization processes and routes to hierarchical assembly, featuring dynamic nanoparticle superlattices and lattices prepared on surfaces or via templating strategies, and explores what one can uniquely learn from and do with colloidal crystals prepared from nucleic acid–functionalized nanomaterials in optics, plasmonics, and catalysis. Volume 4 covers the role of SNAs in biomedicine, especially as diagnostic probes both inside and outside of cells, and treatments based on gene regulation and immunotherapy.

Spherical nucleic acids (SNAs) comprise a nanoparticle core, and a densely packed and highly oriented nucleic acid shell. They have novel structure-dependent properties that differ from those of linear nucleic acids and that makes them useful in chemistry, biology, the life sciences, medicine, materials science, and engineering. This book is a reprint volume that compiles 101 key papers that have been published by the Mirkin Group at Northwestern University, USA, and their collaborators over the past more than two decades. Volume 1 provides an overview and a historical framework of SNAs and discusses their enabling features, which set them apart from all other forms of matter. Volume 2 covers the general design rules for colloidal crystal engineering with DNA, spanning the building blocks and DNA- and RNA-based "programmable bonds" that can be utilized in preparing such structures. Volume 3 continues the discussion of colloidal crystallization processes and routes to hierarchical assembly, featuring dynamic nanoparticle superlattices and lattices prepared on surfaces or via templating strategies, and explores what one can uniquely learn from and do with colloidal crystals prepared from nucleic acid–functionalized nanomaterials in optics, plasmonics, and catalysis. Volume 4 covers the role of SNAs in biomedicine, especially as diagnostic probes both inside and outside of cells, and treatments based on gene regulation and immunotherapy.

This dissertation focuses on the development of biocompatible oligonucleotide-based nanomaterials, known as spherical nucleic acids (SNAs), as therapeutic and diagnostic agents for intracellular gene regulation and in vivo cancer imaging by positron emission tomography (PET). SNAs consist of a nanoparticle core functionalized with a dense shell of oligonucleotides such as deoxyribonucleic acid (DNA). Detailed synthetic procedures and characterization of novel SNAs with purpose-built biocompatible core materials are described. The SNAs exhibit comparable chemical, physical and biological properties regardless of core composition. The functionalities of the SNAs were further tailored by deliberate design and chemical modification of their oligonucleotide sequences.The SNA nanostructures studied in this dissertation include those with cores made from infinite coordination polymers (ICPs), self-assembled block copolymer micelles, 64Cu-alloyed gold nanoclusters, and commercially-available monodisperse gold nanoparticles. In vitro and in vivo investigations of each SNA type are described. The first two examples, functionalized on their surface with DNA, entered a variety of cell lines without the need for transfection agents, and inhibited the translation of disease-related messenger RNA (mRNA). The 64Cu-alloyed gold nanoclusters, functionalized on their surface with either DNA or phosphorodiamidate morpholino (PMO) oligonucleotides, were evaluated in vivo to determine their pharmacokinetics and biodistribution in mice. The blood circulation time of PMO-modified nanoclusters was far superior to DNA-modified nanoclusters, enabling their use in tumor pre-targeting studies wherein a non-radioactive nanocluster was first injected, allowed to accumulate at the tumor site, and then probed by injection of a complementary oligonucleotide labeled with 64Cu. Studies in mouse tumor models demonstrated the feasibility of in vivo hybridization-based pre-targeting using SNA nanomaterials. Furthermore, the basic chemical and biophysical properties of PMO-modified commercial gold nanoparticles were studied. It was determined that PMO-based SNAs display very similar cellular interactions as compared to their DNA analogues, including the capability of entering cells in a transfection-free manner and effecting gene knockdown. The neutral charge of the SNAs based upon PMO oligonucleotides exhibit more rapid capture kinetics of complementary oligonucleotides compared to DNA SNAs, as well as higher melting temperatures of hybridized duplexes. Taken together, the chemical versatility of SNAs has led to significant advances in understanding their basic properties and improving their viability for in vivo translation for biomedical applications.Specifically, we uncovered further evidence for the central hypothesis that the unique properties of SNAs, specifically active cellular uptake and their sharp thermal denaturation curves, are core-independent and rely on the spherical orientation of DNA around a nanoparticle core. We also discovered that the cellular interactions of SNAs, mainly active uptake, are likewise independent of the charge of the nucleic acid shell. However, the chemical composition of the SNA-bound oligonucleotides strongly influences their in vivo pharmacokinetics, with neutral oligonucleotides conferring much longer blood circulation times compared to negatively-charged SNAs. We also found that the kinetics and thermodynamics of hybridization of neutral SNAs to complementary oligonucleotides are superior to those of negatively-charged SNAs, expanding their potential uses not only as biomedical agents but also as in vivo "click chemistry" tools capable of the bioorthogonal connection of multiple components under in vivo physiological conditions. Collectively, the studies presented herein demonstrate that the rational design of the core material and oligonucleotide shell impart novel properties to SNAs that expand their capabilities as therapeutic, diagnostic, and bioorthogonal assembly agents.

This book compiles recent research on the modification of nucleic acids. It covers backbone modifications and conjugation of lipids, peptides and proteins to oligonucleotides and their therapeutic use. Synthesis and application in biomedicine and nanotechnology of aptamers, fluorescent and xeno nucleic acids, DNA repair and artificial DNA are discussed as well.