From Structure to Application: The Evolutionary Trajectory of Spherical Nucleic Acids

Since the proposal of the concept of spherical nucleic acids (SNAs) in 1996, numerous studies have focused on this topic and have achieved great advances. As a new delivery system for nucleic acids, SNAs have advantages over conventional deoxyribonucleic acid (DNA) nanostructures, including independence from transfection reagents, tolerance to nucleases, and lower immune reactions. The flexible structure of SNAs proves that various inorganic or organic materials can be used as the core, and different types of nucleic acids can be conjugated to realize diverse functions and achieve surprising and exciting outcomes. The special DNA nanostructures have been employed for immunomodulation, gene regulation, drug delivery, biosensing, and bioimaging. Despite the lack of rational design strategies, potential cytotoxicity, and structural defects of this technology, various successful examples demonstrate the bright and convincing future of SNAs in fields such as new materials, clinical practice, and pharmacy. Benefiting its structural flexibility, the spherical nucleic acids (SNAs) can be composed of various cores, attachment groups, spacers, and oligonucleotides as a 4D nanostructure. Different compositions of SNAs endow them with different functions and applications, including immunomodulation, gene regulation, drug delivery, biosensing, and bioimaging. With the current challenges solved, SNAs can be a new hopeful material for more areas. image