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.