Membrane-targeted DNA frameworks with biodegradability recover cellular function and morphology from frozen cells.

Cell freezing is critical for the long-term preservation of biological materials, but is limited by the cytotoxicity and inefficacy of conventional cryoprotective agents, such as dimethyl sulfoxide (DMSO). Here, we introduce DNA frameworks (DFs) as a nanoengineered programmable class of cryoprotectants designed to address these challenges. The DFs feature a programmable scaffolded structure offering large flexible wireframe contacts, cellular target ability, and biodegradability. Cholesterol-functionalized DFs outperformed conventional cryoprotectants in the recovery and maintenance of cellular functionality and morphology of frozen cells. Their cryoprotective mechanism enables targeted binding to the cell membrane, minimizing intracellular penetration or uptake, inhibits intracellular and extracellular ice growths, and promotes efficient post-thaw degradation to mitigate toxicity risks. By combining membrane-targeting specificity, cryoprotective efficacy, and biocompatibility, these DFs represent a transformative advance in cell cryopreservation.