Transgene-Free In Vivo Direct Lineage Conversion

 Transdifferentiation is a regenerative medicine approach that directly converts mature somatic cells into lineage-specific cell types using defined transcription factors or gene-regulatory molecules without passing through a pluripotent state. In particular, in vivo transdifferentiation, which reprograms resident cells within damaged tissues into functional target cells, offers a promising strategy for overcoming the limited regenerative capacity of conventional therapies. For example, myocardial infarction causes extensive cardiomyocyte loss and irreversible fibrosis, whereas current treatments primarily prevent further damage and manage disease progression rather than regenerate lost myocardium. Therefore, direct conversion of cardiac fibroblasts into functional cardiomyocytes could enable regeneration of fibrotic cardiac tissue and provide a new therapeutic approach for cardiovascular diseases. Accordingly, our research team aims to develop efficient and safe in vivo transdifferentiation platforms using established protein- and RNA-delivery technologies while minimizing the risks of genomic integration and mutagenesis associated with exogenous DNA.