{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:23Z","timestamp":1792790363493,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,18]]},"group-title":"Bioengineering","reference-count":24,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH\/NHLBI","award":["R01HL171205"],"award-info":[{"award-number":["R01HL171205"]}]},{"name":"MSCRF","award":["2024-MSCRFD-6362"],"award-info":[{"award-number":["2024-MSCRFD-6362"]}],"id":[{"id":"https:\/\/ror.org\/02wpjhe84","id-type":"ROR","asserted-by":"crossref"}]},{"name":"MSCRF","award":["2026-MSCRFL-6569"],"award-info":[{"award-number":["2026-MSCRFL-6569"]}],"id":[{"id":"https:\/\/ror.org\/02wpjhe84","id-type":"ROR","asserted-by":"crossref"}]},{"award":["HI22C0198"],"award-info":[{"award-number":["HI22C0198"]}],"id":[{"id":"https:\/\/ror.org\/00fdzyk40","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Precise correction of pathogenic mutations remains challenging for therapeutic applications because genome editing within protein-coding exons can generate unintended insertion\u2013deletion 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&gt;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.<\/jats:p>","DOI":"10.64898\/2026.09.13.749216","type":"posted-content","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:10:11Z","timestamp":1789801811000},"source":"Crossref","is-referenced-by-count":0,"title":["SEME enables programmable transcript reconstruction through synthetic microexon incorporation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7783-5776","authenticated-orcid":false,"given":"Myeongjune","family":"Go","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewon","family":"Oh","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Cardiovascular Hospital, Cardiovascular Research Institute, Yonsei University College of Medicine; Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunghee","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Systems Informatics and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine; Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine Zhelan","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byunggik","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Suh","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5356-0827","authenticated-orcid":false,"given":"Sangwoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Systems Informatics and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine; Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chulan","family":"Kwon","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7549-9430","authenticated-orcid":false,"given":"Seunghyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092305450514000_2026.09.13.749216v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2015.3"},{"key":"2026092305450514000_2026.09.13.749216v1.2","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s43018-022-00384-z","article-title":"Dysregulation and therapeutic targeting of RNA splicing in cancer","volume":"3","year":"2022","journal-title":"Nat Cancer"},{"key":"2026092305450514000_2026.09.13.749216v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-023-00717-6"},{"key":"2026092305450514000_2026.09.13.749216v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00828-0"},{"key":"2026092305450514000_2026.09.13.749216v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.09.014"},{"key":"2026092305450514000_2026.09.13.749216v1.6","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41467-024-55185-y","article-title":"Systematically developing a registry of splice-site creating variants utilizing massive publicly available transcriptome sequence data","volume":"16","year":"2025","journal-title":"Nat Commun"},{"key":"2026092305450514000_2026.09.13.749216v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0918-899c"},{"key":"2026092305450514000_2026.09.13.749216v1.8","doi-asserted-by":"crossref","unstructured":"F. Allen et al., Predicting the mutations generated by repair of Cas9-induced double-strand breaks. Nat Biotechnol, (2018).","DOI":"10.1101\/400341"},{"key":"2026092305450514000_2026.09.13.749216v1.9","first-page":"79","article-title":"Large DNA deletions occur during DNA repair at 20-fold lower frequency for base editors and prime editors than for Cas9 nucleases","volume":"9","year":"2025","journal-title":"Nat Biomed Eng"},{"key":"2026092305450514000_2026.09.13.749216v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37507-8"},{"key":"2026092305450514000_2026.09.13.749216v1.11","doi-asserted-by":"crossref","first-page":"101901","DOI":"10.1016\/j.xcrm.2024.101901","article-title":"Phase 1\/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy","volume":"6","year":"2025","journal-title":"Cell Rep Med"},{"key":"2026092305450514000_2026.09.13.749216v1.12","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.028382"},{"key":"2026092305450514000_2026.09.13.749216v1.13","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.omtm.2021.05.014","article-title":"A consolidated AAV system for single-cut CRISPR correction of a common Duchenne muscular dystrophy mutation","volume":"22","year":"2021","journal-title":"Mol Ther Methods Clin Dev"},{"key":"2026092305450514000_2026.09.13.749216v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.09.038"},{"key":"2026092305450514000_2026.09.13.749216v1.15","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008873"},{"key":"2026092305450514000_2026.09.13.749216v1.16","first-page":"6","article-title":"Possibilities and limitations of antisense oligonucleotide therapies for the treatment of monogenic disorders","volume":"4","year":"2024","journal-title":"Commun Med (Lond)"},{"key":"2026092305450514000_2026.09.13.749216v1.17","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1021\/acs.biochem.0c00827","article-title":"Structural Perturbations of Exon-Skipping Edits within the Dystrophin D20:24 Region","volume":"60","year":"2021","journal-title":"Biochemistry"},{"key":"2026092305450514000_2026.09.13.749216v1.18","doi-asserted-by":"crossref","first-page":"100334","DOI":"10.1016\/j.xpro.2021.100334","article-title":"Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocytes","volume":"2","year":"2021","journal-title":"STAR Protoc"},{"key":"2026092305450514000_2026.09.13.749216v1.19","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/cvr\/cvae098","article-title":"Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt\/beta-catenin signal pathway","volume":"120","year":"2024","journal-title":"Cardiovasc Res"},{"key":"2026092305450514000_2026.09.13.749216v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/nrm4063"},{"key":"2026092305450514000_2026.09.13.749216v1.21","doi-asserted-by":"crossref","unstructured":"H. Zhong et al., High-fidelity, efficient, and reversible labeling of endogenous proteins using CRISPR-based designer exon insertion. Elife 10, (2021).","DOI":"10.7554\/eLife.64911"},{"key":"2026092305450514000_2026.09.13.749216v1.22","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.120.317076"},{"key":"2026092305450514000_2026.09.13.749216v1.23","doi-asserted-by":"crossref","first-page":"eabk0052","DOI":"10.1126\/sciadv.abk0052","article-title":"Activation of PDGFRA signaling contributes to filamin C-related arrhythmogenic cardiomyopathy","volume":"8","year":"2022","journal-title":"Sci Adv"},{"key":"2026092305450514000_2026.09.13.749216v1.24","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.322750"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.13.749216","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:45:20Z","timestamp":1790167520000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.13.749216"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":24,"URL":"https:\/\/doi.org\/10.64898\/2026.09.13.749216","relation":{},"subject":[],"published":{"date-parts":[[2026,9,18]]},"subtype":"preprint"}}