Carbon Dots as Electrostatically Driven Base-Selective Chemical Compilers for Programmable Nucleic Acid Condensation

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Abstract Cells execute complex biological functions through programmed biomolecular condensation, yet a general and programmable strategy for nucleic acid condensation in vitro remains challenging. Here, we demonstrate that carbon dots (CDs) function as an electrostatic-driven versatile chemical compiler that translates nucleobase sequence into programmed condensate architectures and functions. We found that citric acid-ethylene diamine carbon dots (CA–EDA CDs) drive the condensation of both ssDNA and mRNA via multiple weak interactions. Crucially, the spatially heterogeneous electrostatic potential on the CD surface decodes the distinct electrostatic properties of nucleobases through Coulomb-dominated interactions, establishing a definitive binding hierarchy (G > C > T > A), as revealed by systematic binding studies and molecular dynamics simulations. Based on this chemical compiler, we can achieve hierarchical control of the condensate structure. Furthermore, by programming condensate density via sequence engineering, we achieved switchable up- and down-regulation of GFP mRNA translation in a cell-free system, faithfully mimicking the regulatory role of natural ribonucleoprotein granules. This work establishes CDs as a versatile compiler platform for programmable nucleic acid condensation, transcending the limitations of nonspecific electrostatic neutralization and paving the way for constructing intelligent biomaterials and synthetic biological systems with encoded function.

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