Evidence map›Paper›PMID 41469506›Full record

ArticleCommunications biology2025

In vivo genome editing with a novel Cj4Cas9.

Tianyi Wang, Yafei Tian, Rui Yin, Mengru Li, Jie Luo, Yuan Yang, Chengdong Zhang, Hongyan Chen, Yongming Wang, Daru Lu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. 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.

Tianyi Wang *Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, China.ORCID http://orcid.org/0009-0008-3440-8617
Yafei Tian *State Key Laboratory of Genetics and Development of Complex Phenotypes and MOE Engineering Research Center of Gene Technology, School of Life Sciences and Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China.
Rui YinState Key Laboratory of Genetics and Development of Complex Phenotypes and MOE Engineering Research Center of Gene Technology, School of Life Sciences and Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China.
Mengru LiState Key Laboratory of Genetics and Development of Complex Phenotypes and MOE Engineering Research Center of Gene Technology, School of Life Sciences and Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China.
Jie LuoState Key Laboratory of Genetics and Development of Complex Phenotypes and MOE Engineering Research Center of Gene Technology, School of Life Sciences and Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China.
Yuan YangState Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chengdong ZhangState Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. izhangcd@163.com.
Hongyan ChenState Key Laboratory of Genetics and Development of Complex Phenotypes and MOE Engineering Research Center of Gene Technology, School of Life Sciences and Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China. chenhy@fudan.edu.cn.
Yongming WangCenter for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, China. ymw@fudan.edu.cn.ORCID http://orcid.org/0000-0001-8269-5296
Daru LuState Key Laboratory of Genetics and Development of Complex Phenotypes and MOE Engineering Research Center of Gene Technology, School of Life Sciences and Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China. darulu@163.com.ORCID http://orcid.org/0000-0001-6748-7966

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82070258
6 · The paper itself

Abstract

Natural CRISPR-Cas9 systems provides diverse properties for genome editing, yet finding compact variants remains a priority. In this study, we screened a panel of 11 CjCas9 orthologous using a GFP activation assay and identified seven active nucleases. Among these, Cj4Cas9 stood out as particularly noteworthy due to its compact genome size (985 amino acids) and unique PAM preference (5'-NNNGRY-3'). Cj4Cas9 demonstrates efficient disruption of the Tyr gene in mouse zygotes, resulting in an albino phenotype. Furthermore, when delivered via AAV8, Cj4Cas9 achieves efficient genome editing of the Pcsk9 gene in mouse liver, leading to reduced serum cholesterol and LDL-C levels. Seeking to further expand its utility, we engineered Cj4Cas9 for higher activity by introducing L58Y/D900K mutations, resulting in a variant termed enCj4Cas9. This variant exhibits a two-fold increase in nuclease activity compared to the wild-type Cj4Cas9 and recognizes a simplified N3GG PAM, considerably expanding its targeting scope. These findings establish Cj4Cas9 and its engineered variants for fundamental research and therapeutic applications.

Indexed as

CRISPR-Associated Protein 9CRISPR-Cas SystemsGene EditingAnimalsHumansMiceProprotein Convertase 9CRISPR-Associated Protein 9Pcsk9 protein, mouseProprotein Convertase 9

Identifiers

PMID41469506
PMCPMC12868821

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.