Expanding DdCBE-mediated targeting scope to aC motif preference in rat.

ABSTRACT: An animal model harboring pathogenic mitochondrial DNA (mtDNA) mutations is important to understand the biological links between mtDNA variation and mitochondrial diseases. DdCBE, a DddA-derived cytosine base editor, has been utilized in zebrafish, mice, and rats for tC sequence-context targeting and human mitochondrial disease modeling. However, human pathogenic mtDNA mutations other than the tC context cannot be manipulated. Here, we screened the combination of different DdCBE pairs at pathogenic mtDNA mutation sites with nC (n for a, g, or c) context and identified that the left-G1333C (L1333C) + right G1333N (R1333N) pair could mediate C⋅G-to-T⋅A conversion effectively at aC sites in rat C6 cells. The editing efficiency at disease-associated mtDNA mutation sites within aC context was f

SUBMITTER: Qi X 

PROVIDER: S-EPMC10023868 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature