Single-stranded circular DNA theranostics

The past decade has witnessed the blossom of nucleic acid therapeutics and diagnostics (theranostics). Unlike conventional small molecule medicines or protein biologics, nucleic acid theranostics have characteristic features such as the intrinsic ability as information drugs to code and execute genetic and theranostic information, ready programmability for nucleic acid engineering, intrinsic stimulatory or regulatory immunomodulation, versatile functionalities, and easy conformational recovery upon thermal or chemical denaturation. Single-stranded circular DNA (circDNA) are a class of single-stranded DNAs (ssDNA) featured with their covalently-closed topology. In addition to the basic advantages of nucleic acids-based materials, such as low cost, biocompatibility, and simplicity of chemical modification, the lack of terminals in circDNA prevents exonuclease degradation, resulting in enhanced biostability relative to the corresponding linear ssDNA. circDNA has been explored for versatile theranostic applications. For instance, circDNA has been extensively studied as templates for bioanalytical signal amplification and the synthesis of nano-/micro -/macro-biomaterials via rolling circle amplification (RCA) and rolling circle transcription (RCT) technologies. circDNA has also been commonly used as the scaffolds for the self-assembly of versatile DNA origami. Finally, circDNA has been implemented as theranostic aptamers, miRNA inhibitors, as well as clustered regularly interspaced short palindromic repeats- CRISPR-associated proteins (CRISPR-Cas) gene editing donors. In this review article, we will discuss the chemistry, characteristic properties, and the theranostic applications of circDNA (excluding double-stranded circular DNA such as plasmids); we will also envision the challenges and opportunities in this research field.

Automated summary

The past decade has witnessed significant progress in nucleic acid therapeutics and diagnostics, particularly in the application of single-stranded circular DNA (circDNA). circDNA possesses unique characteristics, such as the ability to encode and execute genetic and theranostic information, easy programmability for engineering, immunomodulation properties, versatile functionalities, and the ability to recover its conformation easily. circDNA has been used in various theranostic applications, including signal amplification in bioanalysis, synthesis of biomaterials, DNA origami self-assembly, and as theranostic agents in gene editing. This review article discusses the chemistry, properties, and applications of circDNA, as well as the challenges and opportunities in this research field.