Genomic DNA locus specified by the ABE8e single-guide RNA (ABE8e target site)

The genomic DNA locus specified by the ABE8e single-guide RNA (sgRNA) refers to the precise chromosomal sequence targeted for nucleotide modification by the Adenine Base Editor 8e (ABE8e) system (Richter et al., 2020, Nature Biotechnology). ABE8e is a CRISPR-derived tool consisting of a catalytically impaired Cas9 nickase (nCas9) fused to an evolved TadA-8e deoxyadenosine deaminase (Gaudelli et al., 2017, Nature). The sgRNA directs the complex to a complementary 20-nucleotide DNA sequence, where the deaminase converts a target adenine (A) to inosine (I) within a specific activity window (Richter et al., 2020, Nature Biotechnology). Because inosine is recognized as guanine (G) by DNA polymerases, this process results in a permanent A•T to G•C base pair transition without the need for double-strand breaks (Newby et al., 2021, Nature). This target is not a single biological entity but rather a class of genomic sites that can be modified to treat genetic diseases or study gene function (Kim et al., 2019, Nature Biotechnology). Therapeutic application requires careful design to avoid bystander editing of adjacent adenines and off-target effects at unintended genomic locations (Kim et al., 2019, Nature Biotechnology).

Other names

CRISPR-Cas9 target siteBase editing locusProtospacer sequenceABE8e-targeted sequenceAdenine base editor target

Adenine deamination leading to A•T to G•C base pair transition