Regulation of Protein Activity and Cellular Functions Mediated by Molecularly Evolved Nucleic Acids

Regulation of protein activity is essential for revealing the molecular mechanisms of biological processes. DNA and RNA achieve many uniquely efficient functions, such as genetic expression and regulation. The chemical capability to synthesize artificial nucleotides can expand the chemical space of nucleic acid libraries and further increase the functional diversity of nucleic acids. Herein, a versatile method has been developed for modular expansion of the chemical space of nucleic acid libraries, thus enabling the generation of aptamers able to regulate protein activity. Specifically, we identify the aptamer targeting integrin alpha3 and show that it can inhibit cell adhesion and migration. Overall, this chemical design‐assisted in vitro selection approach enables the generation of functional nucleic acids for elucidating the molecular basis of biological activities and uncovering a novel basis for the rational design of new protein‐inhibitor pharmaceuticals.

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