High-efficiency base editing for nuclear and mitochondrial DNA with an optimized DYW-like deaminase

Jiyeon Kweon; Soomin Park; Mi Yeon Jeon; Kayeong Lim; Gayoung Jang; An Hee Jang; Minyoung Lee; Cheong Seok; Chaeyeon Lee; Subin Park; Jiseong Ahn; Ji Yoon Jang; Naheun Kim; Young Hoon Sung; Daesik Kim; Yongsub Kim

doi:10.1016/j.ymthe.2025.08.007

High-efficiency base editing for nuclear and mitochondrial DNA with an optimized DYW-like deaminase

Jiyeon Kweon, Soomin Park, Mi Yeon Jeon, Kayeong Lim, Gayoung Jang, An Hee Jang, Minyoung Lee, Cheong Seok, Chaeyeon Lee, Subin Park, Jiseong Ahn, Ji Yoon Jang, Naheun Kim, Young Hoon Sung, Daesik Kim, Yongsub Kim

Research output: Contribution to journal › Article › peer-review

Abstract

CRISPR-based cytosine base editors enable precise genome editing without inducing double-stranded DNA breaks yet traditionally depend on a limited selection of deaminases from the APOBEC/AID or TadA families. Here, we present SsCBE, a CRISPR-based cytosine base editor utilizing SsdA_tox, a DYW-like deaminase derived from the toxin of Pseudomonas syringae. Strategic engineering of SsdA_tox has led to remarkable improvements in the base editing efficiency (by up to 8.4-fold) and specificity for SsCBE, while concurrently reducing cytotoxicity. Exhibiting exceptional versatility, SsCBE was delivered and efficiently applied using diverse delivery methods, including engineered virus-like particles. Its application has enabled targeted cytosine base editing in mouse zygotes and pioneering edits in mitochondrial DNA. SsCBE expands the genome editing toolbox by introducing a distinct deaminase scaffold with broad utility for both basic research and potential therapeutic applications.

Original language	English
Journal	Molecular Therapy
DOIs	https://doi.org/10.1016/j.ymthe.2025.08.007
State	Accepted/In press - 2025
Externally published	Yes

Keywords

CRISPR-Cas
cytosine base editing
DYW-like deaminase
genome engineering

Access to Document

10.1016/j.ymthe.2025.08.007

Cite this

@article{198f2f0b66424a22b0fe25f43c3df445,

title = "High-efficiency base editing for nuclear and mitochondrial DNA with an optimized DYW-like deaminase",

abstract = "CRISPR-based cytosine base editors enable precise genome editing without inducing double-stranded DNA breaks yet traditionally depend on a limited selection of deaminases from the APOBEC/AID or TadA families. Here, we present SsCBE, a CRISPR-based cytosine base editor utilizing SsdAtox, a DYW-like deaminase derived from the toxin of Pseudomonas syringae. Strategic engineering of SsdAtox has led to remarkable improvements in the base editing efficiency (by up to 8.4-fold) and specificity for SsCBE, while concurrently reducing cytotoxicity. Exhibiting exceptional versatility, SsCBE was delivered and efficiently applied using diverse delivery methods, including engineered virus-like particles. Its application has enabled targeted cytosine base editing in mouse zygotes and pioneering edits in mitochondrial DNA. SsCBE expands the genome editing toolbox by introducing a distinct deaminase scaffold with broad utility for both basic research and potential therapeutic applications.",

keywords = "CRISPR-Cas, cytosine base editing, DYW-like deaminase, genome engineering",

author = "Jiyeon Kweon and Soomin Park and Jeon, \{Mi Yeon\} and Kayeong Lim and Gayoung Jang and Jang, \{An Hee\} and Minyoung Lee and Cheong Seok and Chaeyeon Lee and Subin Park and Jiseong Ahn and Jang, \{Ji Yoon\} and Naheun Kim and Sung, \{Young Hoon\} and Daesik Kim and Yongsub Kim",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

doi = "10.1016/j.ymthe.2025.08.007",

language = "English",

journal = "Molecular Therapy",

issn = "1525-0016",

publisher = "Cell Press",

}

TY - JOUR

T1 - High-efficiency base editing for nuclear and mitochondrial DNA with an optimized DYW-like deaminase

AU - Kweon, Jiyeon

AU - Park, Soomin

AU - Jeon, Mi Yeon

AU - Lim, Kayeong

AU - Jang, Gayoung

AU - Jang, An Hee

AU - Lee, Minyoung

AU - Seok, Cheong

AU - Lee, Chaeyeon

AU - Park, Subin

AU - Ahn, Jiseong

AU - Jang, Ji Yoon

AU - Kim, Naheun

AU - Sung, Young Hoon

AU - Kim, Daesik

AU - Kim, Yongsub

PY - 2025

Y1 - 2025

N2 - CRISPR-based cytosine base editors enable precise genome editing without inducing double-stranded DNA breaks yet traditionally depend on a limited selection of deaminases from the APOBEC/AID or TadA families. Here, we present SsCBE, a CRISPR-based cytosine base editor utilizing SsdAtox, a DYW-like deaminase derived from the toxin of Pseudomonas syringae. Strategic engineering of SsdAtox has led to remarkable improvements in the base editing efficiency (by up to 8.4-fold) and specificity for SsCBE, while concurrently reducing cytotoxicity. Exhibiting exceptional versatility, SsCBE was delivered and efficiently applied using diverse delivery methods, including engineered virus-like particles. Its application has enabled targeted cytosine base editing in mouse zygotes and pioneering edits in mitochondrial DNA. SsCBE expands the genome editing toolbox by introducing a distinct deaminase scaffold with broad utility for both basic research and potential therapeutic applications.

AB - CRISPR-based cytosine base editors enable precise genome editing without inducing double-stranded DNA breaks yet traditionally depend on a limited selection of deaminases from the APOBEC/AID or TadA families. Here, we present SsCBE, a CRISPR-based cytosine base editor utilizing SsdAtox, a DYW-like deaminase derived from the toxin of Pseudomonas syringae. Strategic engineering of SsdAtox has led to remarkable improvements in the base editing efficiency (by up to 8.4-fold) and specificity for SsCBE, while concurrently reducing cytotoxicity. Exhibiting exceptional versatility, SsCBE was delivered and efficiently applied using diverse delivery methods, including engineered virus-like particles. Its application has enabled targeted cytosine base editing in mouse zygotes and pioneering edits in mitochondrial DNA. SsCBE expands the genome editing toolbox by introducing a distinct deaminase scaffold with broad utility for both basic research and potential therapeutic applications.

KW - CRISPR-Cas

KW - cytosine base editing

KW - DYW-like deaminase

KW - genome engineering

UR - https://www.scopus.com/pages/publications/105013675606

U2 - 10.1016/j.ymthe.2025.08.007

DO - 10.1016/j.ymthe.2025.08.007

M3 - Article

C2 - 40781772

AN - SCOPUS:105013675606

SN - 1525-0016

JO - Molecular Therapy

JF - Molecular Therapy

ER -

High-efficiency base editing for nuclear and mitochondrial DNA with an optimized DYW-like deaminase

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this