An Integrated Dual‐Functional Nanotool Capable of Studying Single‐Cell Epigenetics and Programmable Gene Regulation

Abstract Single‐cell epigenetics is envisioned to decipher manifold epigenetic phenomena and to contribute to our accurate knowledge about basic epigenetic mechanisms. Engineered nanopipette technology has gained momentum in single‐cell studies; however, solutions to epigenetic questions remain unachieved. This study addresses the challenge by exploring N6‐methyladenine (m 6 A)‐bearing deoxyribozyme (DNAzyme) confined within a nanopipette for profiling a representative m 6 A‐modifying enzyme, fat mass and obesity‐associated protein (FTO). Electroosmotic intracellular extraction of FTO could remove the m 6 A and cause DNAzyme cleavage, leading to the altered ionic current signal. Because the cleavage can release a DNA sequence, we simultaneously program it as an antisense strand against FTO‐mRNA, intracellular injection of which has been shown to induce early stage apoptosis. This nanotool thus features the dual functions of studying single‐cell epigenetics and programmable gene regulation.