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Figure 2—figure supplement 1. Somatic cytosine and adenine base editing at the medaka <italic toggle='yes'>oculocutaneous albinism II (oca2</italic>) gene occurs in the absence of detectable indels and DNA off-target editing.

(a) Translation of sections of exon 6 and 8 of human (Hs), medaka (Ol) and zebrafish (Dr) OCA2 shows high degree of conservation. Amino acids edited or targeted in this study are highlighted in yellow. Missense mutations R305W (green) and A334V (pink) highlight albinism-associated human OCA2 mutations (Kerr et al., 2000; Rebbeck, 2002). (b) Broader window of the Sanger sequencing result displayed in Figure 2e, indicates lack of indels or unwanted editing (Kluesner et al., 2018). (c) Microinjection of oca2 sgRNAs with respective editors at the 1 cell stage causes low levels of aberrant phenotypes in medaka. Abnormal embryos either showed developmental delay or sublethal phenotype, at rates of 6.5%, 6.1%, 17.9%, 10.1%, 3.7%, 9.4%, and 15.8% (left to right), respectively n indicates total number of injected embryos, respectively. (d) The top three DNA off-targets (OTs) as predicted by ACEofBASEs for evoBE4max and ABE8e were evaluated for off-target base editing.

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