Fabrication and Biomedical Applications of "Polymer-Like" Nucleic Acids Enzymatically Produced by Rolling Circle Amplification

Rolling circle amplification (RCA) is an isothermal enzymatic amplification reaction, which is used to massively produce periodic long-single-stranded DNA/RNA with predesigned sequences and functions. The RCA technique not only shows unparalleled advantages in constructing functional DNA assemblies; and the RCA products can also serve as high-performance scaffolds to interact with or accommodate foreign moieties, i.e., therapeutic nucleic acids, proteins, lipids, cationic polymers, and metal nanoparticles (NPs), etc. to fabricate multifunctional and bioresponsive materials with various sizes and morphologies. The RCA product is also a kind of high-molecularweight polyanion with strong inter/intra-molecular interactions, which provides great opportunities for regulating the condensation states of DNA nanomedicines and bulk materials. Based on all these good properties, the RCA-based materials have shown more and more practical potentials in biomedical fields. In this review, we summarize the recent development of RCA-based origami structures, NPs, hydrogels, and metallization, for which the fabrication methods, their biomedical applications, and future prospects are carefully discussed.