# Cytosine base editors with minimized unguided DNA and RNA off-target events and high on-target activity

Article · Yu Y, Leete TC, Born DA, Young L, Barrera LA, Lee SJ, Rees HA, Ciaramella G, Gaudelli NM

- Archive id: doi:10.1038/s41467-020-15887-5
- Published: 2020-04-28
- Venue: Nature communications
- DOI: https://doi.org/10.1038/s41467-020-15887-5
- PMID: 32345976
- PMCID: PMC7189382
- Citations: 168
- Source URL: https://doi.org/10.1038/s41467-020-15887-5
- PDF: https://europepmc.org/articles/PMC7189382/pdf
- Provenance: europepmc

## Abstract

Cytosine base editors (CBEs) enable efficient, programmable reversion of T•A to C•G point mutations in the human genome. Recently, cytosine base editors with rAPOBEC1 were reported to induce unguided cytosine deamination in genomic DNA and cellular RNA. Here we report eight next-generation CBEs (BE4 with either RrA3F \[wt, F130L\], AmAPOBEC1, SsAPOBEC3B \[wt, R54Q\], or PpAPOBEC1 \[wt, H122A, R33A\]) that display comparable DNA on-target editing frequencies, whilst eliciting a 12- to 69-fold reduction in C-to-U edits in the transcriptome, and up to a 45-fold overall reduction in unguided off-target DNA deamination relative to BE4 containing rAPOBEC1. Further, no enrichment of genome-wide C•G to T•A edits are observed in mammalian cells following transfection of mRNA encoding five of these next-generation editors. Taken together, these next-generation CBEs represent a collection of base editing tools for applications in which minimized off-target and high on-target activity are required.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [CRISPR & Gene-Editing Therapies](https://space-kitty.com/topics/gene-editing-therapies)

---
Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.