Evidence map›Paper›PMID 40492429›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Engineered Cas12j-8 is a Versatile Platform for Multiplexed Genome Modulation in Mammalian Cells.

Ru Meng, Jiayao Li, Wuke Wang, Dong Liang, Zhanwei Li, Cong Mao, Qingyang Li, Yu Zhang, Hao Chen, Jin Tang and 5 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
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

15 authors.

Ru MengState Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Jiayao LiState Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Wuke WangThe Key Laboratory of Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
Dong LiangDepartment of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, Jiangsu, 210004, China.
Zhanwei LiHangzhou LUCA Intelligent Technology Co. Ltd., Hangzhou, Zhejiang, 310029, China.
Cong MaoState Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Qingyang LiDepartment of Rare Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
Yu ZhangDepartment of Rare Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
Hao ChenDepartment of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, Jiangsu, 210004, China.
Jin TangHangzhou LUCA Intelligent Technology Co. Ltd., Hangzhou, Zhejiang, 310029, China.
Ping HuDepartment of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, Jiangsu, 210004, China.
Qi NiuDepartment of Rare Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
Xingxu HuangThe Key Laboratory of Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
Bin ShenState Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Jun ZhangState Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.ORCID https://orcid.org/0000-0002-7630-8162

Funding

Creative Research Groups of China 82221005National Key Research and Development Project of China 2022YFC2702705National Natural Science Foundation of China 32371546National Natural Science Foundation of China 81971398National Natural Science Foundation of China 82071434
6 · The paper itself

Abstract

Cas12j-8 is a compact Cas nuclease discovered from the metagenome of giant bacteriophages, consisting of only 717 amino acids and recognizing the '5-TTN-3' protospacer adjacent motif (PAM) sequence. However, its low gene editing efficiency in mammalian cells limits its application in therapeutic gene editing. To address this limitation, structure-guided mutagenesis is employed to replace key negatively charged residues with arginine, strengthening DNA binding. The resulting quintuple mutant, engineered Cas12j-8 (enCas12j-8), demonstrates robust on-target editing efficiency comparable to LbCas12a while maintaining low off-target effects. Cytosine base editors (CBEs) and adenine base editors (ABEs) are developed using enCas12j-8, achieving up to 29.54-fold C-to-T and 36.57-fold A-to-G conversion efficiency compared with the wild-type at the dominated sites, respectively. Notably, enCas12j-8 enables multiplexed editing of three genomic loci simultaneously via a single crRNA array, achieving efficiencies comparable to single-guide approaches. Additionally, enCas12j-8-ABE facilitates the disruption of splice acceptor sites, effectively inducing exon skipping in the SOD1 gene. This strategy holds potential significance for therapeutic genome modulation. These findings establish enCas12j-8 as a versatile, high-precision tool for genome engineering, combining efficient delivery, multiplexing capability, and compatibility with diverse editing modalities.

Indexed as

CRISPR-Associated ProteinsCRISPR-Cas SystemsGene EditingAnimalsHEK293 CellsHumansCRISPR-Associated ProteinsCRISPR‐Cas12j‐8multiplexed editingprotein engineering

Identifiers

PMID40492429
PMCPMC12412624

What OpenQuestion holds

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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.