SEME enables programmable transcript reconstruction through synthetic microexon incorporation

Authors

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

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 20 Sep 2026.

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