Researchers introduced CLASSIC, a method combining long‑ and short‑read sequencing with AI/ML to design, build and map hundreds of thousands to millions of genetic circuit variants in human cells, demonstrating the first large‑scale, AI‑guided genetic-circuit design in a human cell line. The work, published in Nature, paired long‑read sequencing for full-length constructs with short‑read barcoding to enable massively parallel function–sequence mapping. The team generated circuit libraries with fluorescent reporters, transfected human embryonic kidney cells, sorted cells by fluorescence and used sequencing of DNA barcodes plus ML to link sequence to function. Authors said the approach unlocks rapid exploration of genetic design space and is a first demonstration of AI-driven circuit design at scale in mammalian systems. This capability shortens the design cycle for synthetic biology, enabling systematic discovery of DNA designs that implement desired behaviors in human cells and creating a foundation for engineered cell therapies, biosensors and synthetic biology applications.