Fig. 5: Optimizing correction of the PAH R408W variant with a PAM-relaxed ABE.
From: Improved specificity and efficiency of in vivo adenine base editing therapies with hybrid guide RNAs
a, Spacer sequences of PAH4 standard and hybrid gRNAs. rN, ribonucleotide; dN, deoxyribonucleotide; m, 2’-O-methylation; *, phosphorothioate linkage. DNA substitutions are in bold red and underlined. b, A-to-G editing of the PAH on-target site (correction of the R408W variant with or without synonymous bystander editing, or correction plus unwanted nonsynonymous bystander editing) in PAH R408W HuH-7 cells treated with PAH4 standard or hybrid gRNA in combination with SpRY-ABE8.8 mRNA (n = 3 biological replicates per condition). Means are shown. c, Number of sites with a ONE-seq score of >0.01 for each indicated PAH4 standard or hybrid gRNA with SpRY-ABE8.8 protein.