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bioRxiv · 10.64898/2026.09.13.749216

SEME enables programmable transcript reconstruction through synthetic microexon incorporation

Go, M.·Oh, J.·Moon, S.·Chen, E. Z.·Kim, B.·Suh, D.·Kim, S.·Kwon, C.·Lee, S.
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Abstract

Precise correction of pathogenic mutations remains challenging for therapeutic applications because genome editing within protein-coding exons can generate unintended insertion-deletion byproducts that disrupt coding integrity and protein function. To address this limitation, we developed the Spliceable Editable Microexon Element (SEME), an intron-targeting platform that enables programmable microexon incorporation through endogenous splicing. In induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), SEME corrected aberrant splicing caused by the dilated cardiomyopathy-associated FLNC c.2003A>G variant by restoring the five nucleotides missing from exon 12, thereby recovering filamin C expression. Together, these findings establish programmable microexon incorporation as a proof-of-concept strategy for correcting diverse disease-causing transcript defects.

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Go, M., Oh, J., Moon, S., Chen, E. Z., Kim, B., Suh, D., Kim, S., Kwon, C., Lee, S.. 2026-09-18. SEME enables programmable transcript reconstruction through synthetic microexon incorporation. https://doi.org/10.64898/2026.09.13.749216

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