Chemically modified DNA aptamers and DNAzymes for expanded functional capabilities

DNA aptamers and DNAzymes, typically single-stranded DNA (ssDNA), are often selected through systematic evolution of ligands by exponential enrichment (SELEX), and have demonstrated great potential across various applications. However, the inherent properties and limited chemical space of ssDNA pose challenges in terms of stability and functionality. Chemical modifications have emerged as a powerful strategy to enhance the stability and extend the functionality of these molecules. In this review, we summarize the types of chemical modifications applied to DNA aptamers and DNAzymes, and highlight representative examples from the past five years that demonstrate how these modifications expand their functional capabilities. We also discuss the current challenges and future directions in advancing the methodologies and toolsets necessary to accelerate the development of chemically modified functional DNAs, aiming to further broaden their structural diversity, functional complexity, and application potential.