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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.
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References
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Du, Z. et al. Molecular bioengineering of functional nucleic acids. Nat. Rev. Bioeng. https://doi.org/10.1038/s44222-025-00361-y (2025). A review article that presents the functional properties of nucleic acids, with a focus on engineering, optimization and biomedical prospects.
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Tuerk, C. & Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505–510 (1990). This paper reports the technology of systematic evolution of ligands by exponential enrichment (SELEX) for RNA aptamer selection.
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Iwano, N., Adachi, T., Aoki, K., Nakamura, Y. & Hamada, M. Generative aptamer discovery using RaptGen. Nat. Comput. Sci. 2, 378–386 (2022). This paper reports a method that uses a variational autoencoder (VAE) framework with a profile hidden Markov model and SELEX data to design nucleic acid aptamers.
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Zhang, J. et al. Repurposing CRISPR/Cas to discover SARS-CoV-2 detecting and neutralizing aptamers. Adv. Sci. 10, 2300656 (2023). This paper introduces CRISmers, a CRISPR–Cas-based screening system for RNA aptamers that targets a chosen protein of interest in an intracellular context.
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This is a summary of: Zhang, J. et al. Single-round evolution of RNA aptamers with GRAPE-LM. Nat. Biotechnol. https://doi.org/10.1038/s41587-026-03007-5 (2026).
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Generative AI powered by nucleic acid language model enables one-round evolution of RNA aptamers. Nat Biotechnol (2026). https://doi.org/10.1038/s41587-026-03008-4
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DOI: https://doi.org/10.1038/s41587-026-03008-4
