Extended Data Fig. 2. Schematic of Myh6 gene and AAV vector genomes.

A) Schematic of Myh6 gene indicating the location of the pathogenic variant R403Q (numbered according to the human amino acid residues) in exon 13 and the targeted Myh6 mRNA region that was amplified to assess editing (Methods). The locations of reverse transcriptase primer (RT-primer) and PCR primer pairs 1 and 2 are indicated. B) Schematics of dual AAV vector genomes (not to scale) that encode an amino-terminal fragment (N-term) and carboxyl-terminal fragment (C-term) that form base editors after protein splicing. ITR: inverted terminal repeats. Tnnt2 Prom: the cardiomyocyte-specific troponin T promoter. WPRE: Woodchuck hepatitis virus post-transcriptional regulatory element, used to stabilize transcripts. pA-Term: polyadenylation signal and transcriptional terminator. sgRNA: single guide RNA. U6 prom: the human Pol III promoter that efficiently transcribes guide RNAs. C) Schematic of the AAV vector genome used for Cas9 nuclease delivery (not to scale). ITR: Inverted terminal repeats. Tnnt2 prom: the cardiomyocyte specific troponin T promoter. WPRE: Woodchuck hepatitis virus post-transcriptional regulatory element, used to stabilize transcripts. pA-Term: polyadenylation signal and transcriptional terminator. U6 prom: the human Pol III promoter that efficiently transcribes guide RNAs. sgRNA: single guide RNA.