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The CD19 fusion construct is an experimental nucleic acid therapeutic designed to treat cancers harboring mutations in the splicing factor SF3B1, such as acute myeloid leukemia and uveal melanoma. Developed by researchers at Johns Hopkins University and collaborating institutions, the therapy leverages a splicing-dependent mechanism to express targetable cargo specifically in malignant cells. The construct utilizes a synthetic gene fragment from UBA1 containing a cryptic exon that is included in mRNA only in the presence of mutant SF3B1. This engineered plasmid or adeno-associated viral (AAV) vector encodes a fusion protein consisting of the CD44 signal peptide and the CD19 extracellular domain. Upon delivery, the missplicing event triggers the expression of CD19 on the cell surface of SF3B1-mutant cells, effectively "labeling" them for subsequent destruction by anti-CD19 targeted therapies, such as CAR-T cells or monoclonal antibodies.
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