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AAAI 2026

January 24, 2026

Singapore, Singapore

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Biological sequences, including RNAs and proteins, share similarities with natural languages, enabling the application of advanced language models to various biological tasks. However, due to its flexibility and lack of experimental data, RNA is a particularly challenging biological language'' compared to other biological sequences like proteins. RNA multiple sequence alignments (MSAs), which align evolutionarily related RNA sequences, can greatly enhance RNA biology modeling, as evidenced by their significant roles in structure prediction and function annotation. This raises the question of whether RNA MSAs can also benefit RNA design, which remains unexplored. This paper introduces RMSAGen, a model comprising RMSA-Encoder and RMSA-Decoder, that leverages MSAs to design functional RNA sequences. RMSA-Encoder effectively extracts MSA features, enhancing performance in functional prediction and solvent accessibility prediction tasks and supporting RMSA-Decoder in accurate RNA generation. RMSAGen can design RNA-binding protein sequences that effectively bind to target proteins, and the design performance improves with an increasing number of sequences. In addition, the ribozymes designed with structural features by RMSAGen show superior computational metrics and exhibit biological activity during gel electrophoresis. These results highlight effectiveness of RMSAGen, establishing it as a powerful tool and a new direction for RNA design.

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+2Zhiguo Fu
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