Scientists evolve DNA structures that sneak into cells, speeding drug delivery discovery
Researchers developed a screening method that tests thousands of DNA nanostructures simultaneously to find designs cells naturally absorb—a major shortcut for drug developers. The technique uses evolution as a discovery tool, automatically identifying which structures penetrate different cell types, potentially accelerating the pipeline for DNA-based therapeutics from years to months.
Originaltitel: Evolutionary selection of DNA nanostructures for cellular uptake
Abstract DNA nanotechnology offers precise, biocompatible structures with strong potential for targeted drug delivery, yet current discovery approaches rely on testing individual designs, limiting exploration of structural diversity. Here, we introduce an evolutionary selection strategy that screens large libraries of DNA nanostructures, each folded from a single-stranded ‘structure genome’ compatible with amplification and sequencing. Cellular internalization is used as the selection pressure: libraries are incubated with mammalian cells, internalized structures are recovered from lysates, and the process is iterated across multiple rounds in HEK293T and RAW264.7 cells. High-throughput sequencing of recovered structure genomes reveals cell-type-specific enrichment patterns, enabling the identification of individual nanostructures with preferential uptake. Selected candidates were synthesized and evaluated as purified structures, confirming differential internalization by quantitative flow cytometry and microscopy. Turning DNA nanostructure discovery into a selection-based process, could enable high-throughput exploration of structural diversity and provide an alternative route to identify nanostructures with cell-specific uptake properties for biomedical applications.