Key result
In vitro and in silico profiling of base editors demonstrated that approximately 94% of pathogenic C-to-T and T-to-C SNVs can be targeted, with BE4max and hA3A-eBE-Y130F showing high efficiency and dCpf1-eBE yielding high purity.
Why the study?
A variety of base editors have been developed to achieve C-to-T editing in different genomic contexts, but their comparative efficiencies, purity, and accessibilities to pathogenic mutations needed characterization.
This study provides an experimental comparison of cytosine base editors and a comprehensive in silico database (BEable-GPS) to guide the selection of base editors for modeling or correcting pathogenic mutations.
Supports base editor selection for SNV modeling; leaves open in vivo validation before cardiovascular translation.
A variety of base editors have been developed to achieve C-to-T editing in different genomic contexts. Here, we compare a panel of five base editors on their C-to-T editing efficiencies and product purity at commonly editable sites, including some human pathogenic C-to-T mutations. We further profile the accessibilities of 20 base editors to all possible pathogenic mutations in silico. Finally, we build the BEable-GPS (Base Editable prediction of Global Pathogenic SNVs) database for users to select proper base editors to model or correct disease-related mutations. The in vivo comparison and in silico profiling catalog the availability of base editors and their broad applications in biomedical studies.
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Wang et al. (2019) studied Pathogenic single-nucleotide variants (SNVs). Cytosine base editors (BE3, eBE-S3, BE4max, hA3A-eBE-Y130F, dCpf1-eBE) was evaluated on C-to-T editing efficiency and product purity. In vitro and in silico profiling of base editors demonstrated that approximately 94% of pathogenic C-to-T and T-to-C SNVs can be targeted, with BE4max and hA3A-eBE-Y130F showing high efficiency and dCpf1-eBE yielding high purity.
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