Engineering a bacterial toxin deaminase from the DYW-family into a novel cytosine base editor for plants and mammalian cells

verfasst von

Dingbo Zhang, Fiona Parth, Laura Matos da Silva, Teng-Cheong Ha, Axel Schambach, Jens Boch

Abstract

Base editors are precise editing tools that employ deaminases to modify target DNA bases. The DYW-family of cytosine deaminases is structurally and phylogenetically distinct and might be harnessed for genome editing tools. We report a novel CRISPR/Cas9-cytosine base editor using SsdA, a DYW-like deaminase and bacterial toxin. A G103S mutation in SsdA enhances C-to-T editing efficiency while reducing its toxicity. Truncations result in an extraordinarily small enzyme. The SsdA-base editor efficiently converts C-to-T in rice and barley protoplasts and induces mutations in rice plants and mammalian cells. The engineered SsdA is a highly efficient genome editing tool.

Organisationseinheit(en)

Abteilung Pflanzenbiotechnologie
Institut für Pflanzengenetik

Externe Organisation(en)

University of Science and Technology Beijing
Medizinische Hochschule Hannover (MHH)
REBIRTH Forschungszentrum für translationale regenerative Medizin
Harvard Medical School (HMS)

Typ

Artikel

Journal

Genome biology

Band

2025

ISSN

1474-760X

Publikationsdatum

03.02.2025

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

Elektronische Version(en)

https://doi.org/10.1186/s13059-025-03478-w (Zugang: Offen)