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The advent of base editors (BEs) holds great potential for correcting pathogenic-related point mutations to treat relevant diseases. However, Cas9 nickase (nCas9)-derived BEs lead to DNA double-strand breaks, which can trigger unwanted DNA damage response (DDR). Here, we show that the original version of catalytically dead Cas12a (dCas12a)-conjugated BEs induce a basal level of DNA breaks and minimally activate DDR proteins, including H2AX, ATM, ATR, and p53. By fusing dCas12a with engineered human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A), we further develop the BEACON (base editing induced by human APOBEC3A and Cas12a without DNA break) system to achieve enhanced deamination efficiency and editing specificity. Efficient C-to-T editing is achieved by BEACON in mammalian cells at levels comparable to AncBE4max, with only low levels of DDR and minimal RNA off-target mutations. Importantly, BEACON induces in vivo base editing in mouse embryos, and targeted C-to-T conversions are detected in F0 mice.
Pubmed ID: 32492431
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Software for aligning sequencing reads against large reference genome. Consists of three algorithms: BWA-backtrack, BWA-SW and BWA-MEM. First for sequence reads up to 100bp, and other two for longer sequences ranged from 70bp to 1Mbp.
View all literature mentionsSoftware designed to quickly find sequences of 95% and greater similarity of length 25 bases or more.
View all literature mentionsQuality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.
View all literature mentionsCommercial ogranization which provides molecular and drug discovery software and services to researchers. American software company that develops chemical simulation software for use in pharmaceutical, biotechnology, and materials science research. Provides products ranging from general molecular modeling programs to a full suite of chemical simulation and drug design software, including ligand- and structure-based methods.
View all literature mentionsGraph-based alignment of next generation sequencing reads to a population of genomes.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets Phospho-ATR
View all literature mentionsThis polyclonal targets Phospho-p53 (Ser15)
View all literature mentionsThis monoclonal targets ATM protein
View all literature mentionsThis polyclonal targets IgG H&L
View all literature mentionsThis monoclonal targets Histone H2A.X, phospho (Ser139)
View all literature mentionsThis monoclonal targets ATM
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
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