Evidence map›Paper›PMID 42800825›Full record

ArticleGene therapy2026

Rational selection of SpCas9 and variant-derived adenine base editors for human genome editing.

Jiahua Wang, Leben He, Lin Li, Yujing Zhang, Yuanyuan Wang, Yuejun Yang, Zongming Song, Yuanbo Liang, Jin Yang, Feng Gu

Abstract read
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In one paragraph

Article in Gene therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Jiahua Wang *Health Science Center, Changsha Gene Editing Technique Innovation Center, Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, China.
Leben He *Health Science Center, Changsha Gene Editing Technique Innovation Center, Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, China.
Lin LiHealth Science Center, Changsha Gene Editing Technique Innovation Center, Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, China.
Yujing ZhangHealth Science Center, Changsha Gene Editing Technique Innovation Center, Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, China.
Yuanyuan WangHealth Science Center, Changsha Gene Editing Technique Innovation Center, Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, China.
Yuejun YangHealth Science Center, Changsha Gene Editing Technique Innovation Center, Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, China.
Zongming SongHenan Eye Hospital, Henan Eye Institute, Henan Provincial People's Hospital and People's Hospital of Zhengzhou University and People's Hospital of Henan University, Zhengzhou, China.
Yuanbo LiangSchool of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, China.
Jin YangHealth Science Center, Changsha Gene Editing Technique Innovation Center, Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, China. jyang@hunnu.edu.cn.
Feng GuHealth Science Center, Changsha Gene Editing Technique Innovation Center, Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, China. fgu@hunnu.edu.cn.ORCID http://orcid.org/0000-0002-9600-8407

Funding

National Key Research and Development Program of China 2024YFA0917302National Major Science and Technology Projects of China 2023ZD0500502
6 · The paper itself

Abstract

Adenine base editors (ABEs), composed of Cas9 (i.e., SpCas9) nickase, adenosine deaminase, and sgRNA, can convert A•T base pairs to G•C base pairs in the genome without causing DNA double-strand breaks, thereby offering broad application prospects. The strict protospacer adjacent motif requirement and off-target effects of wild-type SpCas9 notably restricted its application until the identification of two SpCas9 variants, SpCas9-NG and SpRY, which have overcome these limitations. However, how to select appropriate ABEs from various SpCas9 variants remains unclear. In this study, we evaluated NGG-ABE8e, NG-ABE8e, and SpRY-ABE8e in human cells and explored the impact of sgRNA design on their performance. The results indicated that NGG-ABE8e showed higher editing activity at most tested NGG-PAM sites, whereas SpRY-ABE8e showed stronger mismatch discrimination and lower detectable A-to-G editing at the selected predicted off-target sites with NGG-PAM sites. Regarding sgRNA design, we found that spacer length and 5' guanine (G) addition affected editing outcomes in a site- and editor-dependent manner. Notably, adding an extra 5' G was not uniformly beneficial and could reduce editing efficiency, especially when the native spacer already began with G. In conclusion, this study provides insights into selecting optimal ABEs and designing effective sgRNAs for the treatment of human genetic diseases.

Identifiers

PMID42800825

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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.