Nature Biotechnology, Published online: 06 February 2026; doi:10.1038/s41587-026-03008-4

GRAPE-LM (generator of RNA aptamers powered by activity-guided evolution and language model) is a generative AI framework that enables the one-round generation of short RNA binders. When guided by CRISPR–Cas-based intracellular screening, GRAPE-LM outperforms traditional multi-round methods for aptamer evolution.