Evidence map›Paper›PMID 37843111›Full record

ArticleNucleic acids research2023

Engineering of cytosine base editors with DNA damage minimization and editing scope diversification.

Bo Yuan, Shuqian Zhang, Liting Song, Jinlong Chen, Jixin Cao, Jiayi Qiu, Zilong Qiu, Jingqi Chen, Xing-Ming Zhao, Tian-Lin Cheng

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Bo YuanInstitute of Pediatrics, National Children's Medical Center, Children's Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.ORCID 0000-0001-6382-1269
Shuqian ZhangInstitute of Pediatrics, National Children's Medical Center, Children's Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
Liting SongInstitute of Science and Technology for Brain-inspired Intelligence, Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China.ORCID 0000-0003-2261-0689
Jinlong ChenInstitute of Pediatrics, National Children's Medical Center, Children's Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
Jixin CaoInstitute of Science and Technology for Brain-inspired Intelligence, Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China.
Jiayi QiuInstitute of Pediatrics, National Children's Medical Center, Children's Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
Zilong QiuInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
Jingqi ChenInstitute of Science and Technology for Brain-inspired Intelligence, Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China.ORCID 0000-0002-2454-0058
Xing-Ming ZhaoInstitute of Science and Technology for Brain-inspired Intelligence, Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China.ORCID 0000-0002-4531-3970
Tian-Lin ChengInstitute of Pediatrics, National Children's Medical Center, Children's Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.ORCID 0000-0002-7376-6600
Fudan University · CNChildren's Hospital of Fudan University · CNChinese Academy of Sciences · CNShanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytosine base editors (CBEs), which enable precise C-to-T substitutions, have been restricted by potential safety risks, including DNA off-target edits, RNA off-target edits and additional genotoxicity such as DNA damages induced by double-strand breaks (DSBs). Though DNA and RNA off-target edits have been ameliorated via various strategies, evaluation and minimization of DSB-associated DNA damage risks for most CBEs remain to be resolved. Here we demonstrate that YE1, an engineered CBE variant with minimized DNA and RNA off-target edits, could induce prominent DSB-associated DNA damage risks, manifested as γH2AX accumulation in human cells. We then perform deaminase engineering for two deaminases lamprey LjCDA1 and human APOBEC3A, and generate divergent CBE variants with eliminated DSB-associated DNA damage risks, in addition to minimized DNA/RNA off-target edits. Furthermore, the editing scopes and sequence preferences of APOBEC3A-derived CBEs could be further diversified by internal fusion strategy. Taken together, this study provides updated evaluation platform for DSB-associated DNA damage risks of CBEs and further generates a series of safer toolkits with diversified editing signatures to expand their applications.

Indexed as

CytosineGene EditingCRISPR-Cas SystemsCytidine DeaminaseDNADNA DamageHumansProteinsRNAAPOBEC3A protein, humanCytidine DeaminaseCytosineDNAProteinsRNA

Identifiers

PMID37843111
PMCPMC10639057
OpenAlexW4387660827

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.