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

Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review

Autorschaft

  • Dingbo Zhang
  • Fiona Parth
  • Laura Matos da Silva
  • Teng-Cheong Ha
  • Jens Boch

Organisationseinheiten

Externe Organisationen

  • University of Science and Technology Beijing
  • Medizinische Hochschule Hannover (MHH)
  • REBIRTH Forschungszentrum für translationale regenerative Medizin
  • Harvard Medical School (HMS)
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  • Mentions
    • News Mentions: 1
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Details

OriginalspracheEnglisch
Aufsatznummer18
FachzeitschriftGenome biology
Jahrgang2025
Ausgabenummer26
PublikationsstatusVeröffentlicht - 3 Feb. 2025

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.

ASJC Scopus Sachgebiete

Zitieren

Engineering a bacterial toxin deaminase from the DYW-family into a novel cytosine base editor for plants and mammalian cells. / Zhang, Dingbo; Parth, Fiona; Matos da Silva, Laura et al.
in: Genome biology, Jahrgang 2025, Nr. 26, 18, 03.02.2025.

Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review

Zhang D, Parth F, Matos da Silva L, Ha TC, Schambach A, Boch J. Engineering a bacterial toxin deaminase from the DYW-family into a novel cytosine base editor for plants and mammalian cells. Genome biology. 2025 Feb 3;2025(26):18. doi: 10.1186/s13059-025-03478-w
Zhang, Dingbo ; Parth, Fiona ; Matos da Silva, Laura et al. / Engineering a bacterial toxin deaminase from the DYW-family into a novel cytosine base editor for plants and mammalian cells. in: Genome biology. 2025 ; Jahrgang 2025, Nr. 26.
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title = "Engineering a bacterial toxin deaminase from the DYW-family into a novel cytosine base editor for plants and mammalian cells",
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.",
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T1 - Engineering a bacterial toxin deaminase from the DYW-family into a novel cytosine base editor for plants and mammalian cells

AU - Zhang, Dingbo

AU - Parth, Fiona

AU - Matos da Silva, Laura

AU - Ha, Teng-Cheong

AU - Schambach, Axel

AU - Boch, Jens

N1 - © 2025. The Author(s).

PY - 2025/2/3

Y1 - 2025/2/3

N2 - 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.

AB - 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.

KW - Gene Editing

KW - Cytosine/metabolism

KW - CRISPR-Cas Systems

KW - Oryza/genetics

KW - Humans

KW - Bacterial Toxins/genetics

KW - Cytosine Deaminase/genetics

KW - Animals

KW - Hordeum/genetics

KW - Protoplasts/metabolism

KW - HEK293 Cells

KW - Mutation

KW - Base editing

KW - Crop improvement

KW - Gene therapy

KW - CRISPR

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U2 - 10.1186/s13059-025-03478-w

DO - 10.1186/s13059-025-03478-w

M3 - Article

C2 - 39901278

VL - 2025

JO - Genome biology

JF - Genome biology

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