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. Author manuscript; available in PMC: 2024 Mar 8.
Published in final edited form as: Nat Biomed Eng. 2023 Dec 6;8(2):118–131. doi: 10.1038/s41551-023-01132-z

Figure 1. Development of adenine base editing to correct SMN2 exon 7 C6T.

Figure 1.

a, Schematic of SMN1 and SMN2 in unaffected individuals and spinal muscular atrophy (SMA) patients. Mutations in SMN1 cause SMA due to a depletion of SMN protein, which may be recovered by editing SMN2. b, Schematic of the SMN2 exon 7 C-to-T (C6T) polymorphism compared to SMN1, with base editor gRNA target sites and their estimated edit windows. c-d, A-to-G editing of SMN2 C6T target adenine and other bystander bases when using ABEs comprised of adenine deaminase domains ABEmax33,38, ABE8.20m35, and ABE8e36 fused to wild-type SpCas9 (panel c) or SpRY37 (panel d), assessed by targeted sequencing. e, A-to-G editing of adenines in SMN2 exon 7 when using SpRY or other relaxed SpCas9 PAM variants44, assessed by targeted sequencing. f, A-to-G editing in exon 7 of SMN2 when using ABE8e-SpG and gRNAs A9 or A10. g, A-to-G editing in exon 7 of SMN2 when using ABE8e-SpRY37 or ABE8e-iSpyMac45 with gRNAs A7 and A8, or wild-type ABE8e-SpCas9 with gRNA A10. Data in panels c-g from experiments in HEK 293T cells; mean, s.e.m., and individual datapoints shown for n = 3 or 4 independent biological replicates.